Supplementary Data

British Journal of Cancer

Inhibition of neurotensin receptor 1 induces intrinsic apoptosis

through let-7a-3p/Bcl-w axis in glioblastoma

Zhen Dong, Qian Lei, Rui Yang, Shunqin Zhu, Xiao-Xue Ke, Liqun Yang, Hongjuan

Cui, and Liang Yi

Supplemental Figures

Supplementary Figure S1 NTSR1 inhibitor SR48692 inhibited cell viability in

glioblastoma cells. (A) Real-time RT–PCR analysis of ntsr1 expression in U87,

LN229, A172 and U251 cells, and a primary glioblastoma tissue 0807T as well as a

counterpart para-carcinoma tissue 0807P. (B) Cells were treated with 0.001, 0.01, 0.1,

1, 10, 100, 1000 μM SR48692 for 48 hours, and inhibition rates were analyzed by

MTT assay. IC50 was calculated by using a GraphPad Prism 6. (C) Image of JC-1

staining in GL261, A172 and U251 glioblastoma cells after treatment of 10μM

SR48692 or DMSO for 48 hours. CCCP treatment groups was used as a positive

control. Scale bars represent 100 μm. All data are shown as the mean ± SD. Student’s

t-test was carried out. ***p < 0.001.

Supplementary Figure S2 (A) Real-time RT–PCR analysis of ntsr1 expression in

A172 and U251 glioblastoma cells after NTSR1 knockdown. (B) Representative

western blot of NTSR1 expression in A172 and U251 glioblastoma cells after NTSR1

knockdown. GAPDH expression levels served as a loading control. (C) Cell viability

assay in A172 and U251 glioblastoma cells after NTSR1 knockdown. All data are

shown as the mean ± SD. Student’s t-test was carried out. **p < 0.01, ***p < 0.001.

Supplementary Figure S3 (A) The effect of Annexin V-FITC/PI dual staining

apoptosis assays analyzed by flow cytometry in A172 and U251 cells after scramble

or NTSR1 knockdown in the presence or absence of 0.5 μM doxorubicin in cultural

medium for 48 hours. (B) The effect of relative caspase 3 activities assays in A172

and U251 cells after scramble or NTSR1 knockdown in the presence or absence of 0.5

μM doxorubicin in cultural medium for 48 hours. 20 μM Ac-DEVD-CHO, a caspase3

inhibitor, was used to perform a negative control. All data are shown as the mean ±

SD. Student’s t-test was carried out. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., no

sense.

Supplementary Figure S4 (A) The effect of Annexin V-FITC/PI dual staining

apoptosis assays analyzed by flow cytometry in 10 μM SR48692 or DMSO-treated

U251 cells after transient transfected with Bcl-w for 48 hours. (B) The effect of

Annexin V-FITC/PI dual staining apoptosis assays analyzed by flow cytometry in

scramble or NTSR1-silenced U251 cells after transient transfected with Bcl-w for 48

hours. All data are shown as the mean ± SD. Student’s t-test was carried out. ***p <

0.001.

scrambleDMSO

shNTSR1#1 scrambleactD

shNTSR1#1

Supplementary Figure S5 Heatmap of microRNA array in U251 cells after NTSR1

knockdown in the absence or presence of actinomycin D in cultural medium for 24

hours.

Supplementary Figure S6 (A) Relative expression of let-7a-3p in A172 and U251

cells after NTSR1 knockdown. (B) Relative expression of let-7a-3p in A172 and

U251 cells after 10 μM SR48692 treatment. (C) Relative expression of let-7a-5p in

A172 and U251 cells after NTSR1 knockdown. (D) Relative expression of let-7a-5p

in A172 and U251 cells after10 μM SR48692 treatment. (E) Relative expression of

c-Myc and LIN28 in A172 and U251 cells after10 μM SR48692 treatment. All data

are shown as the mean ± SD. Student’s t-test was carried out. *p < 0.05, **p < 0.01,

***p < 0.001, n.s., no sense.

Supplementary Figure S7 (A) A172 cells were injected into the flank of BALA/c

nude mice and treated with DMSO or 10mg/kg SR48692 by subcutaneous injection

when tumors were palpable. Mice weight was measured. (B) scramble or

NTSR1-silenced A172 cells were injected into the flank of BALA/c nude mice and

treated with 5μg/kg actinomycin D by subcutaneous injection when tumors were

palpable. Mice weight was measured. All data are shown as the mean ± SD. Student’s

t-test was carried out. *p < 0.05, **p < 0.01, ***p < 0.001.

Supplementary Tables

Supplementary Table S1. RT-PCR primers

Primer

set

Forward Reverse

ntsr1 CGTGGAGCTGTACAACTTCA CAGCCAGCAGACCACAAAGG

c-myc GGGTTCACATGCCCTACACT GGAATCTGGCACTTTTGGCA

lin28 TGATGCAGAAGATCACTCCGTT GGGCTTCCCTCTCGGTTTAT

β-actin CTCTGCTCCTCCTGTTCGAC GCGCCCAATACGACCAAATC

Supplementary Table S2. RNAi target sequences

Target Sequence

shNTSR1#1 AAGAAGTTCATCAGCGCCATC

shNTSR1#2 AACACCTTCATGTCCTTCATA

scramble ATCCGTCCGAACGTAAGTCAA

Supplementary Table S3. PCR primers

Primer set Forward Reverse

Bcl-w CCGGAATTCATGGCGA

CCCCAGCCTCG

CGCGCGGCCGCTCACTTGCTAGCAA

AAAAGGCCC

Supplementary Table S4. Bcl-w 3’UTR sequences

Name Sequence

Bcl-w 3’UTR-wild GGGGGTCTCTGACTTGCTCAGGACAAACTAGGC

CAGTGGTTTTCAAACTGCTTGGCAGAGCCCTGA

AGTTTCCTAGGGGTTGCCTCAGGAGTCCTTGGG

GAGATGAAGGGGGTGGGGAGCTGAGCAGGCTG

GGCAATTTGCCCTCAAACAGAACAGCTCCCCTT

GTAGCGTGATTACATATTGGGGTTCAGGGTAAG

ATTTTATTTGCATTAAGGGGTTTGCTGCTGAAAA

AAAGTTGGAAAACCACTGACTAGACCATCGGCT

CCAAATTGG

Bcl-w 3’UTR-mutant GGGGGTCTCTGACTTGCTCAGGACAAACTAGGC

CAGTGGTTTTCAAACTGCTTGGCAGAGCCCTGA

AGTTTCCTAGGGGTTGCCTCAGGAGTCCTTGGG

GAGATGAAGGGGGTGGGGAGCTGAGCAGGCTG

GGCAATTTGCCCTCAAACAGAACAGCTCCCCTT

GTAGCTGTCTTACATATTGGGGTTCAGGGTAAG

ATTTTATTTGCATTAAGGGGTTTGCTGCTGAAAA

AAAGTTGGAAAACCACTGACTAGACCATCGGCT

CCAAATTGG

Supplementary Table S5. Signal values of RayBio® Human Apoptosis Antibody

Array applied in U251 cells after scramble or NTSR1 knockdown in the presence

or absence of actinomycin D.

name scramble shNTSR1#1 scramble+actD shNTSR1#1+actD p value* p value**

BID 12 11 12 12 11.5 10 12 10 10 11 12 9 0.5072 > 0.9999

BIM 1225 1239 1231.5 1274 1248 1329 1177 1208 1140 1134 1123 1140 0.0990 0.1032

CD40 250 221 239 365.5 375.5 374.5 95 86 91.5 135 159.5 158.5 0.0001 0.0020

CD40L 798 724 776 798 828 788.5 633 632 592 780 734 712 0.1947 0.0070

Caspase3 53 58 55.5 91.5 74.5 88.5 538.5 542 457 1545.5 1524 1452 0.0057 ＜0.0001

DR6 1236 1247 1232 956 1127 1018 910 882 912.5 719 892 877 0.0151 0.2684

Fas 3541 3591 3552 4190 3769.5 3976 3741.5 3681 3761.5 3190 3412.5 3271.5 0.0270 0.0033

FasL 259 307 294.5 179.5 205 189 122 132.5 111.5 98.5 112 108.5 0.0041 0.0980

HSP27 734.5 821 793 659 677 679 743 688 664 542.5 413 472 0.0133 0.0073

HSP60 8532 8589.5 8567.5 17120 13892 14195 14289 13298 14708 16128 13482 15779 0.0032 0.3293

HSP70 2123 2131 2150.5 467 456 435 2328 2390.5 2401.5 3599 3682 3698.5 ＜0.0001 ＜0.0001

HTRA 8902.5 8814 8863.5 7125.5 7893 7790 7823 8220 8340.5 8340.5 8599 8498.5 0.0065 0.1127

IGF-1sR 3123 3434 3252 3654 3289 3580.5 1518 1712 1666.5 1780 1830 1907 0.1721 0.0405

IGF-I 121 201 153 120 135.5 123.5 84 88.5 83.5 88 79.5 89 0.2486 0.9633

IGF-II 588.5 634 613 890 885 840 888 812 837 745 702 703.5 0.0002 0.0082

IGFBP-1 645 534 573 633 682.5 642.5 644.5 623 651.5 480 477 476 0.1281 ＜0.0001

IGFBP-2 1010 835.5 944 2106 2016 2118 439 428.5 418 582.5 599 588 ＜0.0001 ＜0.0001

IGFBP-3 267.5 243.5 229.5 189.5 203 179.5 89 72 61.5 112 114 108.5 0.0125 0.0103

IGFBP-4 189 225 250 143 110.5 120.5 123 138 120.5 98.5 130 100.5 0.0087 0.2045

IGFBP-5 435.5 423 424.5 231 236 246 193.5 134 180 219.5 256 223.5 ＜0.0001 0.0406

IGFBP-6 578 562.5 564.5 489 558.5 504 488 472.5 465.5 433.5 491 457 0.0776 0.4554

SMAC 9345.5 9878.5 9972 15283.5 13489 14438 12378.5 13489 13709.5 10342 13458.5 10257.5 0.0011 0.1791

Survivin 26341 24319 25016 21897.5 24719 23610 2239.5 2139.3 2254.5 3200 3498 3198 0.1473 0.0005

TNF-alpha 513 548 551.5 306 284 296.5 388 372.5 399.5 430 459 441 ＜0.0001 0.0079

TNF-beta 881.5 905.5 903.5 633 645.5 651.5 823.5 845 824.5 634.5 598 614 ＜0.0001 ＜0.0001

TRAILR-1 569.5 496.5 475.5 533.5 502 487 329 324 347 312 379 354.5 0.8510 0.5059

TRAILR-2 134 189.5 156 124 109 105.5 9910 1020.5 9950.5 3456.5 3490 3129.5 0.0515 0.2923

TRAILR-3 10.5 11 9.5 11 8 10 31 33 32 50 52 53.5 0.5360 ＜0.0001

TRAILR-4 486.5 563.5 505 332 378 351 352 345.5 359.5 320.5 335.5 314 0.0035 0.0184

XIAP 19847.5 18934.5 20196.5 30123 31245.5 30920 1422 1388.5 1411.5 3289 3120 3103 ＜0.0001 ＜0.0001

Bad 32.5 31 29 11 11 10 9 8 10 7.5 10 9 ＜0.0001 0.8662

Bax 452.5 498 463.5 472 428 477 356 377 369 356 342.5 340.5 0.5841 0.0549

bcl-2 210.5 235 212 152 144 140 167.5 143 160.5 78 93 89.5 0.0010 0.0012

bcl-w 162.5 178 169.5 78 82 81 137 123 126 80 98 82 < 0.0001 0.0041

cIAP-2 226 238.5 217 122 136 112.5 120.5 134.5 136.5 123 129 137 0.0004 0.9036

caspase8 10.5 8 12 14 11 8 12 12 10 10 11 9 0.7102 0.2051

cytoC 145 132 138 218 228 217 66 65.5 61 74.5 89 85.5 < 0.0001 0.0155

Livin 163.5 159.5 163.5 49 53.5 50 15 13 14 10 8 9 < 0.0001 0.0036

p21 3765.5 3782 3743.5 8124 8208 8137.5 3879 3589.5 3934.5 14590 14328.5 15172 < 0.0001 < 0.0001

p27 297.5 365 330 276 300 279 92.5 87.5 95 228.5 249 250 0.0934 < 0.0001

p53 30128 29987 30074.5 24178 22454 23274 5353 5120 5313 7324.5 7274 7271.5 0.0002 < 0.0001

sTNF-R1 658.5 688 634.5 796 778 796 532 504 502 419.5 423 427 0.0014 0.0008

sTNF-R2 419 459.5 429.5 138 188.5 156 288 196 211 332 267 222.5 0.0001 0.3793

* scramble vs. shNTSR1#1

** scramble+actD vs. shNTSR1#1+actD

Supplementary Table S6. Relative signal values of human microRNA array

applied in U251 cells after scramble or NTSR1 knockdown in the presence or

absence of actinomycin D.

name scramble shNTSR1#1 scramble+actD shNTSR1#1+actD p

value*

p

value**

miR-298 0.892 0.993 1.115 0.321 0.223 0.264 4.982 5.637 5.287 0.452 0.433 0.464 0.0005 < 0.0001

miR-453 0.882 1.103 1.015 0.752 0.783 0.772 0.783 0.803 0.781 0.984 0.932 0.891 0.0236 0.0062

miR-663 0.892 1.104 1.004 0.198 0.245 0.215 7.203 7.123 6.910 0.613 0.635 0.600 0.0002 < 0.0001

miR-675-5p 1.023 0.953 1.024 1.084 0.993 1.043 5.503 5.430 5.618 0.884 0.892 0.844 0.3202 < 0.0001

miR-718 0.934 0.893 1.173 0.221 0.239 0.283 2.359 2.438 2.461 0.263 0.264 0.245 0.0011 < 0.0001

miR-762 1.078 0.945 0.977 1.309 1.189 1.290 1.104 1.128 1.186 0.683 0.694 0.673 0.0086 < 0.0001

let-7a-5p 0.894 0.955 1.151 0.789 0.845 0.820 0.443 0.508 0.456 0.791 0.789 0.746 0.0831 0.0002

let-7a-3p 0.998 0.958 1.044 14.673 18.823 16.156 2.994 3.123 3.083 9.416 10.195 8.444 0.0002 0.0002

let-7b 1.046 1.032 0.922 0.320 0.389 0.370 0.556 0.549 0.549 0.340 0.359 0.307 0.0001 0.0001

let-7c 0.94 0.994 1.066 0.508 0.455 0.447 0.837 0.884 0.868 0.683 0.664 0.681 0.0002 0.0002

let-7d 0.795 1.127 1.078 1.453 1.478 1.410 1.556 1.478 1.579 1.601 1.583 1.603 0.0132 0.1367

let-7e 0.884 0.994 1.122 0.603 0.552 0.583 0.883 0.863 0.861 1.173 1.183 1.178 0.0039 < 0.0001

let-7f 1.092 1.034 0.874 0.903 0.826 0.835 0.893 0.793 0.870 1.144 1.237 1.143 0.1049 0.0018

let-7g-5p 0.886 0.992 1.122 0.443 0.394 0.401 1.339 1.324 1.323 1.045 1.022 1.060 0.0011 < 0.0001

let-7g-3p 0.984 1.109 0.907 0.612 0.689 0.666 0.538 0.525 0.538 0.573 0.723 0.564 0.0055 0.1706

let-7i-5p 0.956 0.985 1.059 0.384 0.438 0.400 0.992 0.973 0.957 0.887 0.894 0.866 < 0.0001 0.0022

let-7i-3p 0.924 0.992 1.084 0.705 0.793 0.773 0.835 0.823 0.822 0.989 1.045 0.911 0.0105 0.0166

miR-100 1.071 0.975 0.954 0.583 0.672 0.603 2.132 2.098 2.111 0.772 0.890 0.722 0.0011 < 0.0001

miR-103 1.082 1.023 0.895 1.289 1.324 1.316 2.189 2.342 2.585 2.335 2.458 2.343 0.0053 0.9590

miR-106a-5p 1.011 1.048 0.941 1.777 1.554 1.681 2.327 2.184 2.191 2.334 2.198 2.233 0.0007 0.7514

miR-106a-3p 1.019 1.048 0.933 1.932 1.610 1.792 2.219 1.093 2.198 1.375 1.428 1.441 0.0014 0.3205

miR-106b-5p 1.061 0.932 1.007 1.427 1.623 1.576 3.004 3.126 2.924 2.384 2.295 2.249 0.0015 0.0006

miR-106b-3p 0.083 0.994 1.923 0.589 0.683 0.665 0.378 0.421 0.391 1.302 1.149 1.291 0.5418 < 0.0001

miR-107 0.998 0.98 1.022 0.465 0.423 0.439 0.618 0.643 0.631 0.458 0.448 0.442 < 0.0001 < 0.0001

miR-10a 1.034 0.979 0.987 0.772 0.734 0.742 1.004 1.008 0.933 1.097 1.038 1.086 0.0003 0.0388

miR-10b 1.041 0.993 0.966 0.774 0.765 0.775 2.192 1.428 1.751 0.694 0.683 0.688 0.0005 0.0076

miR-1197 0.984 0.893 1.123 0.284 0.342 0.303 2.231 2.321 2.179 0.629 0.518 0.514 0.0006 < 0.0001

miR-122-5p 0.972 0.895 1.133 0.507 0.449 0.474 5.221 4.668 5.219 2.893 2.945 2.944 0.0019 0.0003

miR-122-3p 0.918 1.045 1.037 0.603 0.504 0.559 1.386 1.438 1.415 0.891 0.930 0.823 0.0009 0.0001

miR-124-3p 0.91 1.082 1.008 0.012 0.008 0.010 0.443 0.349 0.424 0.081 0.043 0.014 < 0.0001 0.0005

miR-125a-3p 0.951 1.074 0.975 1.302 1.232 1.224 1.332 1.034 1.154 0.983 1.129 1.101 0.0050 0.3529

miR-125a-5p 0.955 1.098 0.947 1.205 1.258 1.232 0.775 0.746 0.782 0.836 0.983 0.865 0.0108 0.0517

miR-125b-3p 0.942 0.993 1.065 1.004 0.835 0.973 1.023 1.102 1.165 0.738 0.718 0.769 0.3763 0.0012

miR-125b-5p 0.955 0.93 1.115 0.865 0.821 0.841 1.304 1.203 1.181 1.132 1.093 1.131 0.0565 0.0505

miR-126-3p 0.957 0.945 1.098 2.109 2.543 2.359 3.320 3.043 3.029 2.549 2.451 2.658 0.0006 0.0067

miR-126-5p 1.023 0.942 1.035 0.225 0.240 0.228 1.773 1.568 1.740 0.597 0.583 0.589 < 0.0001 < 0.0001

miR-1281 1.045 0.974 0.981 0.583 0.515 0.521 11.320 10.932 11.955 2.331 2.355 2.435 0.0001 < 0.0001

miR-129-3p 1.052 0.892 1.056 0.745 0.802 0.784 0.128 0.203 0.167 0.329 0.209 0.210 0.0169 0.1399

miR-129-5p 0.993 1.034 0.973 0.887 0.914 0.904 3.134 2.894 3.030 1.218 1.097 1.101 0.0074 < 0.0001

miR-130a 1.034 0.983 0.983 0.254 0.202 0.232 0.781 0.614 0.606 0.184 1.203 0.199 < 0.0001 0.7065

miR-130b 1.041 0.979 0.98 0.134 0.112 0.129 1.818 1.893 1.863 0.242 0.136 0.142 < 0.0001 < 0.0001

miR-132 1.011 0.894 1.095 3.023 3.419 3.279 6.302 6.230 5.986 5.672 5.416 5.627 < 0.0001 0.0084

miR-135b-5p 1.047 0.887 1.066 1.225 1.378 1.338 0.892 0.833 0.822 0.719 0.732 0.726 0.0126 0.0050

miR-135b-3p 1.083 0.918 0.999 1.223 1.089 1.111 1.134 1.523 1.627 1.384 1.459 1.466 0.0894 0.9590

miR-138 1.032 0.925 1.043 1.235 1.119 1.222 1.004 0.893 1.030 0.884 0.938 0.913 0.0217 0.2264

miR-139-3p 0.991 1.038 0.971 0.342 0.315 0.322 1.034 1.009 1.179 0.418 0.443 0.439 < 0.0001 0.0003

miR-139-5p 0.999 1.092 0.909 1.359 1.132 1.290 1.112 1.231 1.280 0.908 0.892 0.909 0.0382 0.0037

miR-140 1 0.993 1.007 0.780 0.834 0.805 1.123 1.099 1.098 0.746 0.774 0.745 0.0003 < 0.0001

miR-141-3p 0.989 1.023 0.988 0.815 0.845 0.816 1.892 1.752 1.992 3.987 3.617 4.038 0.0003 0.0002

miR-141-5p 0.928 1.042 1.03 0.212 0.235 0.222 1.345 1.945 1.972 0.917 0.993 0.892 < 0.0001 0.0166

miR-142-3p 1.096 0.78 1.124 0.756 0.783 0.772 1.233 2.435 2.525 2.098 1.976 2.086 0.1064 0.9803

miR-142-5p 1.023 0.994 0.983 1.052 0.899 1.056 0.456 0.573 0.552 0.321 0.332 0.307 0.9670 0.0049

miR-143 1.103 0.982 0.915 0.583 0.702 0.689 0.432 0.342 0.321 0.295 0.328 0.294 0.0068 0.1731

miR-144 1.037 0.943 1.02 2.003 1.943 1.937 1.221 1.219 1.379 4.737 4.253 4.742 < 0.0001 < 0.0001

miR-145-5p 0.992 0.993 1.015 0.205 0.296 0.287 1.453 1.421 1.566 0.817 0.823 0.808 < 0.0001 0.0001

miR-1469 0.883 1.025 1.092 0.994 1.013 1.057 5.462 5.385 5.618 1.217 1.283 1.120 0.7570 < 0.0001

miR-146a 1.032 1.01 0.958 1.452 1.221 1.367 0.723 0.827 0.741 0.386 0.746 0.758 0.0081 0.3492

miR-146b-5p 1.045 1.024 0.931 0.203 0.225 0.195 1.002 1.045 1.067 0.185 0.203 0.183 < 0.0001 < 0.0001

miR-146b-3p 1.081 0.994 0.925 2.044 2.055 2.038 1.213 1.093 1.174 2.974 3.041 2.749 < 0.0001 < 0.0001

miR-147 0.892 1.061 1.047 2.504 2.336 2.468 2.003 2.132 2.140 2.001 1.930 2.077 < 0.0001 0.2209

miR-148a-3p 1.045 0.98 0.975 0.678 0.784 0.768 2.138 1.985 2.034 0.993 0.732 0.908 0.0030 0.0002

miR-148a-5p 0.789 1.026 1.185 0.045 0.083 0.072 1.234 1.323 1.343 0.112 0.114 0.116 0.0013 < 0.0001

miR-148b-3p 0.873 1.092 1.035 0.488 0.535 0.513 1.004 0.934 0.907 0.538 0.554 0.524 0.0019 0.0002

miR-148b-5p 0.998 1.055 0.999 1.045 1.052 1.033 0.482 0.655 0.600 0.793 0.775 0.794 0.2561 0.0154

miR-149 0.884 1.032 1.084 0.146 0.138 0.136 1.558 1.443 1.654 0.402 0.332 0.408 0.0001 < 0.0001

miR-150-5p 0.845 1.065 1.09 0.572 0.508 0.569 2.132 1.221 2.192 1.208 1.184 1.201 0.005 0.1071

miR-150-3p 0.877 1.023 1.1 0.671 0.655 0.666 1.893 2.345 2.704 0.784 0.775 0.796 0.0069 0.0029

miR-151-3p 1.077 1.022 0.901 0.673 0.653 0.676 2.783 2.226 2.866 1.428 1.482 1.550 0.0032 0.0051

miR-151-5p 1.099 0.99 0.911 0.702 0.640 0.684 0.892 1.032 0.920 0.583 0.593 0.596 0.0049 0.0011

miR-152 0.993 0.775 1.232 0.344 0.321 0.311 0.885 0.721 0.553 0.172 0.184 0.174 0.0070 0.0048

miR-154 0.987 0.994 1.019 0.665 0.603 0.624 0.332 0.293 0.280 0.233 0.203 0.186 < 0.0001 0.0105

miR-155 0.912 1.12 0.968 1.883 1.822 1.843 1.982 1.452 1.795 5.128 5.002 6.205 0.0002 0.0008

miR-15a-5p 0.923 1.312 0.765 2.341 2.672 2.512 1.337 1.328 1.341 0.799 0.983 0.744 0.0013 0.0024

miR-15a-3p 1.09 0.993 0.917 2.044 3.199 2.056 1.321 1.274 1.217 1.429 1.448 1.482 0.0207 0.0057

miR-15b-5p 1.003 0.83 1.167 0.224 0.402 0.383 0.884 0.714 0.712 0.592 0.438 0.461 0.0041 0.0215

miR-15b-3p 1.035 1.003 0.962 0.683 0.402 0.673 1.002 1.442 1.079 0.403 0.441 0.408 0.0118 0.0051

miR-16-1 0.984 0.83 1.186 0.442 0.459 0.443 1.034 1.321 1.284 0.628 0.647 0.676 0.0059 0.0035

miR-16-1-3p 0.996 0.956 1.048 0.506 0.634 0.447 1.821 1.784 1.841 0.884 0.982 0.887 0.0015 < 0.0001

miR-16-2-3p 0.925 1.042 1.033 1.456 1.438 1.376 1.632 1.347 1.562 1.453 1.618 1.649 0.0007 0.6007

miR-17-5p 1.008 0.987 1.005 0.447 0.700 0.482 1.283 1.221 1.273 0.423 0.214 0.485 0.0045 0.0005

miR-17-3p 1.023 1.034 0.943 2.109 1.835 2.218 0.663 0.615 0.648 1.904 1.626 1.943 0.0009 0.0003

miR-181a 1.03 1.032 0.938 0.668 0.759 0.649 1.223 1.043 1.041 0.735 0.788 0.762 0.0026 0.0054

miR-181b 1.039 0.993 0.968 0.735 0.874 0.739 0.934 1.003 0.903 0.771 0.782 0.642 0.0123 0.0162

miR-181c 0.993 0.934 1.073 2.667 2.785 2.558 3.320 3.231 3.383 3.788 3.209 3.697 < 0.0001 0.2429

miR-181d 0.984 0.927 1.089 0.243 0.229 0.225 1.232 1.221 1.285 0.997 1.138 0.952 < 0.0001 0.0217

miR-182 0.967 1.094 0.939 1.457 1.592 1.521 0.883 0.874 0.857 1.102 1.307 1.109 0.0011 0.0112

miR-183-5p 0.923 1.12 0.957 1.032 1.039 0.949 0.739 0.732 0.703 0.348 0.495 0.413 0.9259 0.0022

miR-183-3p 0.994 1.223 0.783 2.443 2.884 2.604 4.856 4.382 4.750 0.692 1.346 0.880 0.0008 0.0001

miR-184 0.782 1.094 1.124 0.020 0.018 0.005 0.456 0.536 0.428 0.038 0.119 0.011 0.0008 0.0008

miR-185 0.795 1.123 1.082 0.834 0.902 0.848 0.993 0.932 0.936 0.893 1.004 0.981 0.2580 0.8919

miR-186-5p 1.096 0.967 0.937 0.805 0.723 0.746 1.253 1.372 1.376 0.756 0.734 0.747 0.0114 0.0001

miR-186-3p 1.009 0.992 0.999 0.658 0.795 0.694 0.335 0.372 0.352 0.329 0.432 0.338 0.0023 0.7198

miR-187 1.003 0.923 1.074 0.251 0.398 0.220 3.528 3.438 3.414 0.517 0.629 0.760 0.0005 < 0.0001

miR-18a-5p 1.045 0.924 1.031 1.345 1.332 1.359 1.672 1.783 1.880 1.293 1.213 1.212 0.0009 0.0012

miR-18a-3p 0.973 1.003 1.024 0.993 0.892 0.991 0.893 1.023 0.806 0.703 0.736 0.704 0.3205 0.0393

miR-18b 0.945 1.045 1.01 3.341 3.954 3.201 1.003 1.042 1.044 2.004 2.194 3.066 0.0004 0.0131

miR-191-5p 1.094 0.892 1.014 0.882 1.092 0.896 0.892 0.873 0.837 0.783 0.776 0.778 0.6542 0.0056

miR-191-3p 1.093 0.884 1.023 0.255 0.263 0.276 1.212 1.093 1.127 0.548 0.553 0.631 0.0003 0.0002

miR-193b 0.943 1.004 1.053 0.927 1.003 0.967 1.763 1.582 1.636 1.648 1.638 1.653 0.4246 0.8076

miR-194 0.928 1.093 0.979 1.793 1.893 1.869 3.329 3.098 3.293 4.008 3.896 4.034 0.0001 0.0009

miR-195-5p 0.942 1.034 1.024 1.845 1.782 2.100 6.823 7.890 7.440 8.784 8.229 8.631 0.0009 0.0294

miR-195-3p 1.094 1.003 0.903 0.189 0.234 0.147 1.023 0.992 0.957 0.324 0.402 0.313 0.0002 < 0.0001

miR-196a 1.094 0.934 0.972 0.190 0.193 0.179 0.672 0.583 0.606 0.349 0.421 0.340 < 0.0001 0.0025

miR-196b 1.096 0.975 0.929 0.882 0.725 0.776 1.201 1.205 1.232 0.774 0.784 0.672 0.0389 0.0002

miR-198 0.934 0.983 1.083 0.672 0.683 0.690 1.572 1.882 1.747 2.086 2.381 2.059 0.0020 0.0320

miR-199b-3p 1.032 0.993 0.975 5221 4.523 4.218 6.334 6.273 6.439 7.482 6.894 7.532 0.0003 0.0106

miR-199a-3p 1.095 1.034 0.871 0.532 0.553 0.525 1.123 1.112 1.170 0.304 0.657 0.620 0.0023 0.0058

miR-199a-5p 0.883 0.993 1.124 0.255 0.265 0.260 0.893 0.735 0.790 0.783 0.658 0.636 0.0004 0.1558

miR-199b-5p 0.892 0.943 1.165 0.294 0.308 0.289 0.482 0.338 0.372 0.782 0.927 0.741 0.0011 0.0042

miR-19a 0.984 1.045 0.971 1.783 1.632 1.684 1.598 1.814 1.847 1.329 1.238 1.371 0.0001 0.0073

miR-19b 0.994 1.033 0.973 0.883 0.793 0.825 0.409 0.384 0.410 0.514 0.505 0.514 0.0063 0.0003

miR-200a-3p 0.782 1.112 1.106 0.935 0.994 0.929 2.013 2.118 2.228 3.219 3.198 3.337 0.6917 0.0001

miR-200a-5p 0.773 1.098 1.129 0.520 0.538 0.504 0.552 0.504 0.502 0.443 0.451 0.436 0.0138 0.0109

miR-200b-3p 0.68 1.201 1.119 0.993 0.932 0.940 1.012 1.230 1.116 2.148 2.098 2.152 0.7960 0.0001

miR-200b-5p 0.932 0.993 1.075 1.102 1.099 1.069 1.932 1.893 2.217 1.034 1.003 1.041 0.1030 0.0007

miR-200c-3p 0.56 1.307 1.133 2.103 1.994 1.969 1.231 1.034 1.303 1.098 1.002 1.099 0.0112 0.2285

miR-200c-5p 0.893 1.093 1.014 0.578 0.583 0.569 1.182 1.093 1.191 0.938 0.945 0.953 0.0019 0.0027

miR-202-3p 0.789 1.023 1.188 0.021 0.013 0.001 0.384 0.321 0.344 0.043 0.015 0.034 0.0010 < 0.0001

miR-202-5p 1.093 1.003 0.904 1.215 1.334 1.204 1.345 1.582 1.468 0.783 0.773 0.791 0.0216 0.0006

miR-204 1.124 0.933 0.943 0.206 0.221 0.181 0.832 0.452 0.739 0.302 0.227 0.226 0.0002 0.0226

miR-205 1.332 0.783 0.885 0.163 0.158 0.151 0.032 0.230 0.170 0.054 0.038 0.048 0.0075 0.1732

miR-206 1.093 0.955 0.952 4.203 4.321 4.238 3.321 3.582 3.388 12.309 11.237 12.056 < 0.0001 < 0.0001

miR-208b 1.212 0.821 0.967 0.394 0.455 0.451 4.592 4.772 4.700 0.803 0.784 0.865 0.0081 < 0.0001

miR-20a-5p 0.987 1.034 0.979 0.663 0.672 0.694 1.132 1.324 1.341 0.989 0.938 0.920 < 0.0001 0.0107

miR-20a-3p 1.007 1.003 0.99 0.502 0.457 0.485 1.592 1.482 1.548 1.528 1.556 1.525 < 0.0001 0.9032

miR-20b-5p 1.034 0.996 0.97 0.835 0.856 0.848 1.672 1.667 1.638 1.250 1.237 1.236 0.0014 < 0.0001

miR-20b-3p 1.213 0.773 1.014 0.934 0.793 0.800 0.443 0.345 0.319 1.308 1.295 1.386 0.3084 < 0.0001

miR-21-5p 1.435 0.789 0.776 0.645 0.693 0.680 1.325 1.321 1.297 1.023 1.003 0.926 0.2076 0.0006

miR-21-3p 1.032 0.934 1.034 1.503 1.427 1.475 0.882 0.903 0.888 0.538 0.783 0.536 0.0003 0.0297

miR-210 1.127 1.003 0.87 0.245 0.266 0.280 0.382 0.345 0.373 0.303 0.285 0.297 0.0006 0.0044

miR-211 1.156 0.787 1.057 1.020 1.003 1.017 2.414 2.519 2.512 1.098 1.045 1.080 0.9097 < 0.0001

miR-212-3p 0.984 0.993 1.023 0.803 0.732 0.726 2.394 2.243 2.326 1.892 1.845 1.833 0.0008 0.0006

miR-214-5p 1.045 1.034 0.921 1.283 1.209 1.277 1.628 1.842 1.544 1.457 1.442 1.427 0.0052 0.0618

miR-214-5p 0.995 1.034 0.971 0.604 0.559 0.597 1.342 1.034 1.135 0.889 0.783 0.889 < 0.0001 0.0312

miR-218 0.995 0.993 1.012 1.512 1.603 1.532 2.349 2.043 2.186 2.378 2.428 2.395 < 0.0001 0.0814

miR-219-3p 1.038 1.034 0.928 1.284 1.327 1.311 5.987 6.592 7.478 3.128 3.228 3.106 0.0013 0.0012

miR-219-5p 0.932 0.993 1.075 1.506 1.458 1.485 1.203 1.219 1.108 2.021 2.349 2.021 0.0004 0.0011

miR-22-3p 0.895 1.104 1.001 0.998 1.023 0.976 1.782 1.432 1.899 1.687 1.765 1.694 0.9879 0.9422

miR-22-5p 0.886 1.204 0.91 1.034 0.997 1.064 1.921 1.367 1.219 1.198 1.207 1.184 0.7761 0.2255

miR-221 0.889 0.994 1.117 1.257 1.389 1.347 1.342 1.453 1.440 1.302 1.302 1.200 0.0124 0.0423

miR-222 1.191 0.893 0.916 0.893 0.884 0.983 2.132 2.093 2.061 0.893 0.804 0.799 0.4719 < 0.0001

miR-223 1.033 0.994 0.973 0.534 0.603 0.583 0.823 0.753 0.778 3.872 3.338 3.877 < 0.0001 < 0.0001

miR-23a-3p 1.112 0.887 1.001 1.045 1.120 1.075 1.382 1.232 1.332 1.984 1.804 1.787 0.3078 0.0021

miR-23a-5p 1.233 0.773 0.994 0.982 0.930 0.903 0.652 0.452 0.499 0.465 0.563 0.514 0.6712 0.7756

miR-23b-3p 1.021 0.982 0.997 0.258 0.305 0.293 0.788 0.883 0.837 0.402 0.372 0.360 < 0.0001 0.0001

miR-23b-5p 0.893 0.998 1.109 0.405 0.423 0.404 2.030 2.119 1.989 0.619 0.462 0.647 0.0007 < 0.0001

miR-24-1 0.923 0.884 1.193 0.745 0.773 0.740 0.939 0.832 0.881 0.773 0.673 0.778 0.0645 0.0364

miR-24-1-5p 0.789 1.088 1.123 1.324 1.204 1.203 0.342 0.482 0.450 0.730 0.674 0.735 0.0980 0.0035

miR-24-2-5p 1.134 1.043 0.823 0.593 0.525 0.582 0.873 0.834 0.776 0.354 0.503 0.453 0.0102 0.0017

miR-25 1.209 0.884 0.907 0.398 0.337 0.383 1.293 1.092 1.180 0.775 0.745 0.749 0.0041 0.0018

miR-26a-1 1.176 0.832 0.992 0.789 0.945 0.738 4.582 4.536 4.424 1.093 1.294 1.089 0.2078 < 0.0001

miR-26a-1-3p 1.111 1.003 0.886 0.305 0.286 0.284 0.807 0.774 0.794 0.518 0.428 0.424 0.0004 0.0005

miR-26a-2-3p 0.992 0.889 1.119 1.136 1.205 1.116 1.263 1.236 1.180 1.032 1.003 1.012 0.1011 0.0012

miR-26b-5p 0.978 0.934 1.088 0.442 0.435 0.423 1.025 0.932 1.075 0.894 0.864 0.878 0.0003 0.0367

miR-26b-3p 0.834 0.998 1.168 0.523 0.672 0.556 0.542 0.438 0.347 0.328 0.784 0.338 0.0174 0.8110

miR-27a-3p 0.845 1.084 1.071 0.568 0.479 0.463 1.672 1.682 1.546 0.764 0.548 0.544 0.0041 0.0003

miR-27a-5p 0.56 1.233 1.207 1.044 1.032 1.052 0.821 0.938 0.711 1.428 1.273 1.410 0.8558 0.0026

miR-27b-3p 0.792 1.134 1.074 0.342 0.285 0.236 1.623 1.923 1.531 1.293 0.946 1.014 0.0029 0.0187

miR-27b-5p 0.899 1.045 1.056 4.123 3.895 3.935 0.048 0.432 0.165 0.894 0.893 0.793 < 0.0001 0.0055

miR-28-3p 0.993 1.003 1.004 0.884 0.795 0.883 2.784 2.332 2.258 1.328 1.295 1.324 0.0080 0.0023

miR-28-5p 1.034 0.882 1.084 0.744 0.844 0.731 1.289 1.128 1.222 1.023 1.034 1.048 0.0322 0.0197

miR-2861 1.127 0.88 0.993 0.250 0.244 0.248 4.372 4.668 4.118 0.189 0.139 0.200 0.0005 < 0.0001

miR-296-3p 0.994 0.934 1.072 1.253 1.255 1.253 0.734 0.717 0.738 1.201 1.034 1.009 0.0032 0.0044

miR-296-5p 0.873 1.026 1.101 0.684 0.625 0.639 0.572 0.600 0.574 0.342 0.336 0.387 0.0072 0.0003

miR-297a 0.805 0.994 1.201 0.376 0.391 0.381 3.203 2.773 2.951 2.884 2.339 2.870 0.0057 0.2722

miR-29a-3p 0.904 0.893 1.203 1.578 1.489 1.510 5.093 5.226 5.070 3.747 3.294 3.744 0.0075 0.0006

miR-29a-5p 1.09 0.993 0.917 0.219 0.243 0.231 0.827 0.883 0.825 0.783 0.875 0.729 0.0001 0.3501

miR-29b-1 1.188 1.004 0.808 0.673 0.665 0.662 2.371 2.982 2.383 2.103 1.904 2.026 0.0385 0.0538

miR-29b-1-5p 1.117 0.843 1.04 0.703 0.782 0.696 4.482 4.128 4.158 1.805 1.884 1.787 0.0339 < 0.0001

miR-29c-3p 1.124 0.993 0.883 0.505 0.496 0.483 2.240 2.389 2.338 1.532 1.604 1.526 0.0019 0.0001

miR-29c-5p 1.157 1.032 0.811 1.306 1.336 1.266 2.478 3.213 3.257 0.994 0.978 0.933 0.0427 0.0014

miR-300 1.021 1.034 0.945 0.457 0.420 0.444 4.328 4.582 4.564 1.123 1.245 1.106 < 0.0001 < 0.0001

miR-301a 0.993 0.889 1.118 0.198 0.157 0.175 0.923 0.819 0.805 0.548 0.492 0.496 0.0003 0.0012

miR-301b 0.924 1.032 1.044 1.003 0.894 0.984 1.275 1.138 1.149 0.917 0.837 0.842 0.4790 0.0032

miR-302a 0.893 1.123 0.984 0.903 0.993 0.903 3.746 3.336 3.335 1.128 1.284 1.297 0.4124 0.0001

miR-302b 0.995 1.193 0.812 0.238 0.243 0.228 0.652 0.558 0.549 0.628 0.664 0.638 0.0023 0.1752

miR-302c 1.094 0.893 1.013 2.634 2.468 2.501 7.682 8.172 8.310 4.889 4.927 4.976 < 0.0001 < 0.0001

miR-302d 1.034 0.872 1.094 0.667 0.568 0.640 0.231 0.273 0.223 0.184 0.175 0.161 0.0067 0.0150

miR-30a-5p 0.786 1.099 1.115 0.603 0.683 0.676 1.386 1.672 1.472 0.573 0.527 0.576 0.0348 0.0004

miR-30a-3p 0.892 1.183 0.925 0.243 0.436 0.362 1.667 1.538 1.536 0.645 0.633 0.635 0.0038 < 0.0001

miR-30b-5p 0.994 0.937 1.069 3.135 3.459 3.233 2.093 2.030 1.901 4.728 8.193 4.742 < 0.0001 0.0283

miR-30b-3p 1.093 0.782 1.125 0.794 0.883 0.802 2.070 1.983 1.813 0.993 0.892 0.996 0.1992 0.0003

miR-30c-5p 0.782 1.231 0.987 0.542 0.572 0.571 1.894 1.775 1.774 0.503 0.465 0.491 0.0281 < 0.0001

miR-30c-1-3p 0.774 1.188 1.038 1.633 1.673 1.665 0.768 0.569 0.665 0.845 0.814 0.878 0.0057 0.0418

miR-30d 1.045 0.934 1.021 0.374 0.325 0.353 1.280 1.230 1.160 0.455 0.543 0.482 < 0.0001 < 0.0001

miR-30e-5p 1.213 0.788 0.999 1.178 1.098 1.146 1.750 1.736 1.568 1.132 1.302 1.307 0.3230 0.0059

miR-30e-3p 1.024 0.878 1.098 0.757 0.746 0.759 1.645 1.535 1.457 0.639 0.589 0.641 0.0191 < 0.0001

miR-31-5p 0.562 1.231 1.207 0.778 0.805 0.797 1.239 1.021 1.017 0.719 0.992 0.988 0.3993 0.1731

miR-31-3p 0.789 1.134 1.077 0.747 0.792 0.793 1.368 1.429 1.460 1.128 1.136 1.147 0.1079 0.0005

miR-311-5p 0.893 1.092 1.015 0.782 0.840 0.887 2.347 2.226 2.295 1.034 1.042 0.967 0.0666 < 0.0001

miR-32 0.652 1.231 1.117 0.403 0.394 0.349 0.783 0.875 0.894 1.112 1.136 1.104 0.0255 0.0017

miR-323-5p 0.77 1.254 0.976 0.442 0.419 0.431 3.297 3.676 3.876 0.892 0.993 0.905 0.0154 < 0.0001

miR-324-3p 0.777 1.135 1.088 1.329 1.230 1.138 0.849 0.990 0.979 0.884 0.891 0.876 0.1369 0.2882

miR-324-5p 1.034 0.874 1.092 0.895 1.005 0.969 0.634 0.754 0.635 0.773 0.873 0.773 0.589 0.0639

miR-325 1.126 1.005 0.869 0.720 0.683 0.674 10.023 9.294 9.660 2.415 2.443 2.355 0.0152 < 0.0001

miR-326 1.032 0.845 1.123 0.535 0.569 0.525 2.998 3.004 3.091 2.135 2.242 2.362 0.0053 0.0004

miR-328 1.032 0.937 1.031 0.510 0.552 0.490 1.658 1.573 1.587 0.365 0.375 0.357 0.0002 < 0.0001

miR-329 1.177 0.992 0.831 0.483 0.506 0.501 1.231 1.433 1.135 0.720 0.728 0.710 0.0074 0.0034

miR-331-3p 1.124 0.893 0.983 1.008 0.984 0.978 0.664 0.773 0.672 0.583 0.428 0.656 0.8900 0.1239

miR-335-3p 0.994 1.005 1.001 1.386 1.518 1.483 1.563 1.446 1.471 2.034 2.132 2.155 0.0003 0.0003

miR-335-5p 0.984 1.034 0.982 1.368 1.348 1.047 1.071 1.008 1.072 0.782 0.565 0.680 0.0730 0.0048

miR-337-3p 0.789 1.088 1.123 0.649 0.598 0.642 3.256 3.445 3.320 2.104 2.303 2.076 0.0259 0.0002

miR-337-5p 1.124 0.993 0.883 0.478 0.538 0.465 2.673 2.776 2.629 1.458 1.673 1.554 0.0023 0.0001

miR-338-3p 1.287 0.783 0.93 2.603 2.587 2.523 11.324 8.788 10.854 11.283 10.739 12.749 0.0005 0.2666

miR-338-5p 0.829 0.993 1.178 0.520 0.730 0.863 12.893 13.232 13.929 4.102 4.338 3.985 0.1056 < 0.0001

miR-339-3p 0.878 1.024 1.098 1.402 1.248 1.259 2.891 1.896 2.128 1.329 1.258 1.312 0.0205 0.0289

miR-339-5p 0.979 1.167 0.854 0.603 0.598 0.788 1.223 1.413 1.314 0.738 0.775 0.769 0.0379 0.0006

miR-33b-5p 0.836 0.895 1.269 1.439 1.443 1.439 0.306 0.337 0.298 0.124 0.324 0.147 0.0314 0.1473

miR-33b-3p 1.204 0.884 0.912 1.304 1.495 1.192 1.437 1.336 1.362 0.917 0.883 0.801 0.0710 0.0004

miR-340-3p 1.106 0.888 1.006 0.583 0.556 0.548 0.562 0.633 0.494 0.538 0.243 0.587 0.0024 0.4036

miR-340-5p 1.004 0.887 1.109 0.503 0.445 0.478 6.735 6.223 6.637 4.329 4.327 4.222 0.0014 0.0002

miR-342-3p 1.009 0.893 1.098 1.407 1.309 1.350 0.997 0.878 0.753 1.502 1.443 1.459 0.0057 0.0012

miR-342-5p 1.109 0.934 0.957 0.895 1.040 0.909 1.232 1.336 1.383 1.673 1.478 1.566 0.5087 0.0238

miR-345-5p 0.542 1.178 1.28 0.231 0.229 0.267 4.656 4.568 5.263 1.890 2.093 2.110 0.0306 0.0003

miR-346 0.846 1.193 0.961 0.773 0.740 0.739 0.418 0.390 0.337 0.347 0.429 0.435 0.0721 0.5842

miR-34a 1.073 0.983 0.944 0.395 0.420 0.387 0.630 0.552 0.515 0.398 0.329 0.309 0.0001 0.0070

miR-34c-5p 0.996 0.993 1.011 0.615 0.599 0.605 0.327 0.986 0.206 0.183 0.205 0.185 < 0.0001 0.2633

miR-34c-3p 1.056 1.034 0.91 0.482 0.429 0.436 1.002 0.783 0.944 0.628 0.618 0.619 0.0003 0.0118

miR-363-3p 1.038 1.003 0.959 0.298 0.373 0.319 1.738 1.308 1.662 0.329 0.336 0.340 < 0.0001 0.0007

miR-365 0.976 0.984 1.04 1.034 1.134 1.098 1.347 1.450 1.366 1.902 1.929 1.908 0.0669 < 0.0001

miR-369-3p 0.966 1.044 0.99 0.045 0.024 0.038 0.306 0.375 0.229 0.048 0.058 0.057 < 0.0001 0.0042

miR-369-5p 1.046 0.993 0.961 0.559 0.482 0.515 1.008 1.378 1.020 0.983 1.085 0.968 0.0001 0.3859

miR-370 0.892 0.935 1.173 0.840 0.867 0.865 1.109 1.326 1.109 1.293 1.283 1.350 0.1796 0.1660

miR-371-3p 0.888 1.034 1.078 0.730 0.691 0.706 4.375 5.820 5.073 1.664 1.932 1.630 0.0076 0.0014

miR-372 0.873 0.983 1.144 0.375 0.321 0.350 1.730 1.448 1.891 0.375 0.638 0.451 0.0013 0.0014

miR-373-3p 0.984 0.799 1.217 0.462 0.477 0.461 2.678 2.884 3.007 0.718 0.755 0.781 0.0116 < 0.0001

miR-373-5p 1.093 0.884 1.023 1.285 1.382 1.316 1.784 2.074 1.982 0.665 0.587 0.553 0.0084 0.0001

miR-375 1.034 0.987 0.979 1.238 1.382 1.370 5.337 4.899 5.452 0.735 0.682 0.665 0.0026 < 0.0001

miR-376a 0.762 0.873 1.365 0.471 0.449 0.461 1.114 1.420 1.550 0.783 0.628 0.696 0.0436 0.0085

miR-376b 1.074 0.887 1.039 0.379 0.345 0.375 3.418 2.337 2.982 0.671 0.732 0.742 0.0004 0.0022

miR-376c 0.872 1.034 1.094 0.288 0.213 0.232 1.242 1.194 1.286 0.238 0.339 0.321 0.0004 < 0.0001

miR-377 0.998 1.034 0.968 1.592 1.402 1.461 3.897 4.014 4.018 2.318 1.984 2.065 0.0012 < 0.0001

miR-378-3p 0.689 1.067 1.244 0.472 0.433 0.455 1.183 1.094 1.188 0.482 0.583 0.480 0.0291 0.0002

miR-378-5p 0.865 1.134 1.001 0.342 0.330 0.323 2.639 2.459 2.514 1.128 1.098 1.150 0.0010 < 0.0001

miR-379 0.855 1.133 1.012 0.663 0.683 0.701 1.319 1.492 1.318 1.219 1.137 1.310 0.0174 0.1136

miR-380-3p 0.947 1.198 0.855 3.128 3.521 3.125 2.338 2.469 2.613 11.340 12.093 12.106 0.0002 < 0.0001

miR-380-5p 1.092 1.035 0.873 1.613 1.582 1.633 0.503 0.488 0.490 2.447 2.116 2.552 0.0008 0.0001

miR-381 1.032 0.893 1.075 0.301 0.289 0.263 1.765 1.738 1.776 0.475 0.775 0.548 0.0002 0.0002

miR-382 1.043 0.885 1.072 0.349 0.338 0.384 2.194 1.895 2.095 0.338 0.473 0.564 0.0004 0.0001

miR-409-3p 0.994 1.056 0.95 0.984 1.034 1.007 1.002 1.390 1.095 0.812 0.839 0.801 0.8183 0.0426

miR-409-5p 1.094 0.978 0.928 0.568 0.683 0.683 1.523 1.674 1.535 2.127 2.098 2.121 0.0047 0.0004

miR-410 0.945 1.034 1.021 0.542 0.535 0.525 0.183 0.227 0.213 0.124 0.092 0.143 < 0.0001 0.0112

miR-411 0.917 0.887 1.196 0.184 0.163 0.179 1.232 1.163 1.167 0.159 0.189 0.232 0.0011 < 0.0001

miR-412 0.925 0.778 1.297 3.192 3.002 2.999 3.046 3.333 3.319 2.123 2.461 2.244 0.0002 0.0022

miR-421 0.996 1.143 0.861 0.128 0.159 0.136 0.894 0.885 0.865 0.384 0.465 0.345 0.0005 0.0002

miR-422a 1.042 0.995 0.963 0.182 0.230 0.172 3.546 3.217 3.461 3.448 3.284 3.445 < 0.0001 0.8960

miR-422b 1.032 0.893 1.075 0.782 0.689 0.739 4.195 4.238 4.116 2.775 3.094 2.760 0.0126 0.0003

miR-423-3p 1.139 0.874 0.987 0.773 0.585 0.636 0.680 0.854 0.663 0.532 0.642 0.554 0.0243 0.0882

miR-423-5p 1.001 1.025 0.974 0.430 0.335 0.354 2.339 2.417 2.401 0.439 0.482 0.490 < 0.0001 < 0.0001

miR-424-3p 0.893 0.893 1.214 1.040 1.359 1.043 0.715 0.984 0.826 1.094 0.894 1.062 0.3830 0.1540

miR-425-5p 0.884 1.022 1.094 0.664 0.618 0.624 1.293 1.329 1.296 0.582 0.615 0.517 0.0045 < 0.0001

miR-425-3p 0.762 1.135 1.103 1.342 1.225 1.246 0.726 0.618 0.662 1.728 1.739 1.709 0.0954 < 0.0001

miR-429 0.692 1.235 1.073 0.995 0.894 0.997 0.129 0.158 0.175 1.893 1.946 1.965 0.8286 < 0.0001

miR-432 0.993 0.893 1.114 0.520 0.535 0.463 49.320 52.374 55.818 2.875 2.346 2.867 0.0019 < 0.0001

miR-433 1.044 0.886 1.07 0.430 0.410 0.382 6.334 6.873 6.706 0.503 0.547 0.539 0.0006 < 0.0001

miR-449a 1.049 0.873 1.078 0.694 0.782 0.700 0.953 0.887 0.900 1.028 1.038 1.021 0.0172 0.0051

miR-449b 1.121 0.788 1.091 1.134 1.120 1.062 1.638 1.634 1.622 0.719 0.673 0.729 0.3871 < 0.0001

miR-450a-5p 1.094 0.862 1.044 0.415 0.473 0.425 4.653 4.286 4.527 0.384 0.382 0.362 0.0015 < 0.0001

miR-450b-5p 0.943 0.865 1.192 0.983 0.899 0.960 2.395 2.451 2.369 1.098 1.902 1.044 0.6320 0.0192

miR-451 0.978 0.882 1.14 0.344 0.354 0.352 0.917 0.831 0.946 0.883 0.874 0.903 0.0010 0.7660

miR-452-5p 1.036 1.004 0.96 1.781 1.923 1.853 1.785 1.549 1.703 1.218 1.320 1.201 < 0.0001 0.0053

miR-454 1.032 1.135 0.833 0.395 0.420 0.371 1.329 1.354 1.345 1.372 1.985 1.737 0.0025 0.1169

miR-455-3p 0.879 1.023 1.098 0.549 0.556 0.545 0.994 0.985 0.898 1.473 1.573 1.369 0.0022 0.0015

miR-455-5p 1.049 1.099 0.852 0.083 0.092 0.079 1.000 1.328 1.087 0.984 0.643 0.565 0.0003 0.0654

miR-483-3p 1.123 1.008 0.869 0.253 0.349 0.243 8.982 7.437 8.819 0.482 0.674 0.539 0.0009 < 0.0001

miR-483-5p 1.087 1.01 0.903 0.773 0.715 0.719 6.332 6.345 6.519 1.784 1.983 1.837 0.0095 0.0001

miR-489 0.947 1.036 1.017 0.205 0.140 0.214 2.328 2.234 2.222 0.899 0.873 0.898 < 0.0001 < 0.0001

miR-492 0.977 0.779 1.244 0.291 0.234 0.240 7.430 7.519 7.356 1.784 1.938 1.954 0.0054 < 0.0001

miR-493-3p 1.043 0.945 1.012 0.567 0.549 0.576 1.049 1.038 1.050 1.232 1.438 1.178 0.0001 0.0404

miR-493-5p 0.984 0.877 1.139 2.194 2.224 2.221 1.783 1.900 1.978 4.096 3.895 4.099 < 0.0001 < 0.0001

miR-494 1.093 0.888 1.019 16.138 15.229 15.137 18.931 16.782 19.109 23.183 24.782 24.822 < 0.0001 0.0029

miR-495 0.992 1.034 0.974 0.834 0.881 0.833 0.401 0.394 0.402 0.338 0.374 0.397 0.0032 0.1662

miR-496 0.889 1.099 1.012 0.592 0.682 0.604 0.444 0.438 0.433 0.515 0.718 0.518 0.0051 0.0968

miR-497-5p 0.778 1.132 1.09 0.567 0.572 0.541 1.083 1.309 1.280 0.592 0.691 0.524 0.0172 0.0019

miR-497-3p 1.095 1.023 0.882 0.448 0.439 0.427 0.794 0.745 0.788 0.340 0.216 0.252 0.0009 0.0002

miR-498 1.128 1.004 0.868 1.020 1.003 4.000 3.228 3.574 3.565 0.972 0.874 0.979 0.3702 < 0.0001

miR-499-3p 1.093 1.05 0.857 0.238 0.281 0.259 4.291 4.457 4.540 0.917 0.703 0.712 0.0005 < 0.0001

miR-499-5p 0.983 1.004 1.013 0.293 0.301 0.289 2.105 2.136 2.156 0.805 0.872 0.805 < 0.0001 < 0.0001

miR-501-3p 0.937 0.883 1.18 1.749 1.734 1.751 1.713 1.645 1.669 1.983 1.775 1.883 0.0012 0.0318

miR-501-5p 1.134 1.12 0.746 1.213 0.834 1.237 1.849 1.845 1.854 1.836 1.884 1.929 0.6307 0.2801

miR-503 1.045 0.894 1.061 4.294 3.893 4.412 1.349 1.349 1.388 1.345 1.463 1.589 < 0.0001 0.2214

miR-504 1.031 0.883 1.086 0.442 0.350 0.513 0.329 0.342 0.152 0.221 0.302 0.205 0.0018 0.6667

miR-505-3p 0.983 0.892 1.125 1.023 1.342 1.296 1.291 1.228 1.265 0.573 0.632 0.691 0.1413 < 0.0001

miR-506 1.094 1.034 0.872 0.341 0.221 0.139 11.213 13.084 12.162 1.443 1.453 1.453 0.0010 < 0.0001

miR-508-3p 0.883 1.003 1.114 2.010 1.823 1.714 1.732 1.743 1.663 0.354 0.387 0.357 0.0015 < 0.0001

miR-508-5p 0.874 1.03 1.096 0.456 0.582 0.542 4.005 4.025 4.079 0.548 0.593 0.534 0.0033 < 0.0001

miR-512-5p 0.884 1.102 1.014 0.324 0.305 0.299 1.848 1.784 1.899 0.892 0.884 0.854 0.0004 < 0.0001

miR-518f 0.928 1.003 1.069 0.538 0.558 0.539 3.672 3.749 3.792 1.232 1.319 1.300 0.0004 < 0.0001

miR-519a-5p 0.983 1.112 0.905 0.562 0.466 0.467 3.385 3.274 3.377 1.223 1.681 0.854 0.0018 0.0016

miR-520b 1.033 1.033 0.934 3.167 3.542 2.181 31.230 32.783 31.932 46.783 48.927 51.203 0.0085 0.0002

miR-520g 1.004 0.755 1.241 0.428 0.495 0.462 2.380 2.310 2.314 1.642 1.633 1.942 0.0191 0.0046

miR-523 1.045 0.889 1.066 0.333 0.345 0.323 1.482 1.576 1.576 0.428 0.458 0.624 0.0003 0.0002

miR-524-3p 1.096 0.937 0.967 0.529 0.619 0.600 3.872 3.479 3.744 2.374 2.557 2.533 0.0017 0.0007

miR-524-5p 0.945 0.997 1.058 1.034 1.003 1.021 2.008 2.138 2.116 1.384 1.842 1.756 0.5987 0.0433

miR-526a 0.937 0.885 1.178 1.348 1.342 1.231 1.947 1.894 1.953 1.428 1.468 1.412 0.0350 < 0.0001

miR-527 1.056 0.789 1.155 1.515 1.452 1.546 2.135 2.095 2.147 1.983 1.789 1.848 0.0110 0.0133

miR-557 1.085 0.899 1.016 1.004 1.339 0.904 3.894 3.295 3.591 1.732 1.563 1.426 0.5939 0.0005

miR-572 0.994 0.782 1.224 0.345 0.420 0.377 4.339 4.782 4.915 0.342 0.439 0.331 0.0088 < 0.0001

miR-583 0.982 0.784 1.234 2.329 1.284 2.235 2.517 2.673 2.545 2.193 2.087 2.195 0.0570 0.0022

miR-584 0.847 0.883 1.27 0.402 0.443 0.399 3.226 3.872 3.812 0.894 0.884 0.894 0.0127 0.0002

miR-586 1.046 1.021 0.933 0.302 0.334 0.277 0.338 0.325 0.323 0.093 0.132 0.081 < 0.0001 0.0001

miR-602 0.983 1.223 0.794 0.883 0.520 0.832 3.229 3.418 3.275 0.993 1.093 0.915 0.2040 < 0.0001

miR-612 1.034 1.033 0.933 0.554 0.602 0.470 8.977 8.554 8.685 2.884 3.095 2.953 0.0009 < 0.0001

miR-615-3p 1.034 1.043 0.923 1.223 1.340 1.262 1.032 1.284 1.041 0.935 0.894 0.906 0.0060 0.0678

miR-615-5p 0.994 0.883 1.123 1.109 1.231 1.123 0.673 0.518 0.604 0.515 0.534 0.500 0.1236 0.1486

miR-616-3p 0.967 0.897 1.136 0.653 0.821 0.625 4.253 4.315 4.235 0.438 0.232 0.232 0.0327 < 0.0001

miR-616-5p 0.912 0.846 1.242 0.443 0.458 0.459 1.477 1.837 1.613 1.983 1.894 1.827 0.0112 0.0860

miR-623 0.919 0.876 1.205 1.023 0.834 0.835 0.983 0.684 0.694 0.745 0.774 0.689 0.4435 0.6407

miR-625 1.094 1.076 0.83 0.789 0.832 0.756 2.136 2.174 2.297 1.856 1.998 1.914 0.0776 0.0118

miR-628-3p 0.903 1.034 1.063 0.338 0.342 0.365 1.369 1.358 1.463 2.394 2.784 2.124 0.0002 0.0059

miR-628-5p 0.994 1.145 0.861 2.668 2.331 2.630 1.459 1.440 1.595 1.894 1.984 1.852 0.0003 0.0027

miR-638 1.093 1.132 0.775 0.183 0.293 0.204 3.654 3.563 3.351 0.303 0.254 0.204 0.0028 < 0.0001

miR-658 1.083 1.008 0.909 0.042 0.034 0.030 3.129 3.330 3.172 0.043 0.056 0.042 < 0.0001 < 0.0001

miR-659 1.037 1.01 0.953 0.673 0.772 0.745 4.884 4.137 4.398 1.283 1.098 1.069 0.0022 0.0001

miR-671-3p 0.903 1.005 1.092 0.203 0.320 0.199 0.340 0.371 0.355 0.321 0.232 0.289 0.0004 0.0534

miR-671-5p 1.094 0.786 1.12 0.220 0.219 0.216 0.754 0.894 0.766 0.231 0.131 0.282 0.0019 0.0007

miR-674-5p 1.034 1.13 0.836 0.440 0.482 0.467 2.385 2.481 2.340 1.319 1.273 1.039 0.0036 0.0002

miR-674-3p 0.992 1.201 0.807 1.459 1.553 1.552 45.730 42.190 47.084 40.621 38.183 43.902 0.0115 0.1369

miR-675b 1.034 1.004 0.962 0.549 0.630 0.595 5.374 5.237 5.226 0.772 0.894 0.985 0.0002 < 0.0001

miR-711 0.893 1.335 0.772 0.782 0.773 0.759 4.987 5.112 5.186 1.983 2.309 2.012 0.2527 < 0.0001

miR-758 0.782 1.112 1.106 0.384 0.556 0.284 1.444 1.528 1.438 1.239 1.113 1.152 0.0118 0.0031

miR-769-3p 1.055 1.034 0.911 1.893 1.450 1.977 4.886 3.462 4.491 1.328 1.342 1.324 0.0103 0.0023

miR-769-5p 1.066 0.878 1.056 0.814 0.773 0.800 5.447 7.226 6.111 1.714 1.775 1.723 0.0304 0.0010

miR-770-5p 1.134 0.844 1.022 1.203 1.004 1.005 1.578 1.193 1.719 0.402 0.364 0.393 0.5460 0.0021

miR-875-3p 0.811 0.84 1.349 0.308 0.225 0.284 3.427 3.385 3.357 1.643 1.917 1.982 0.0146 0.0001

miR-875-5p 0.882 0.892 1.226 0.453 0.543 0.583 0.631 0.616 0.618 0.382 0.783 0.347 0.0166 0.4478

miR-877 0.893 0.934 1.173 0.920 0.884 0.892 3.187 3.209 3.445 1.672 1.485 1.729 0.3136 0.0001

miR-9-5p 0.679 1.321 1 1.819 1.783 1.801 0.351 0.448 0.451 0.984 0.843 0.790 0.0125 0.0024

miR-9-3p 0.665 1.224 1.111 0.539 0.673 0.592 0.638 0.627 0.624 0.405 0.332 0.319 0.0850 0.0005

miR-92a 0.782 1.12 1.098 0.892 0.812 0.822 0.635 0.614 0.649 0.718 0.772 0.719 0.2313 0.0072

miR-92b 0.832 1.087 1.081 0.566 0.672 0.670 0.456 0.673 0.554 0.537 0.512 0.544 0.0161 0.6612

miR-93-5p 1.008 0.993 0.999 1.432 1.223 1.223 5.213 5.099 5.080 1.232 1.382 1.280 0.0138 < 0.0001

miR-93-3p 1.003 1.121 0.876 1.195 1.238 1.227 0.985 1.094 0.950 1.349 1.673 1.574 0.0377 0.0077

miR-95 1.104 1.036 0.86 1.332 1.320 1.291 4.883 5.209 4.956 7.873 7.674 7.695 0.0130 < 0.0001

miR-96 1.112 1.332 0.556 0.783 0.743 0.767 1.142 1.462 1.146 1.231 1.322 1.346 0.3657 0.6794

miR-98 1.093 0.892 1.015 0.784 0.772 0.731 2.438 2.459 2.431 2.336 2.873 2.856 0.0173 0.2362

miR-99a 0.776 1.232 0.992 1.805 1.743 1.701 2.113 2.094 2.188 1.923 1.883 1.927 0.0052 0.0023

miR-99b-5p 0.789 1.11 1.101 1.332 1.302 1.293 0.934 0.780 0.859 0.984 0.973 0.901 0.0437 0.1390

miR-99b-3p 0.893 1.078 1.029 1.432 1.335 1.336 0.893 0.864 0.862 1.002 1.094 1.027 0.0046 0.0045

* scramble vs. shNTSR1#1

** scramble+actD vs. shNTSR1#1+actD