Supplementary Table S1. List of miRNAs on human 3p and the changes of their genome copies determined by genomic real-time PCR.

Change of frequency, ID Accession Chromosome Start End Strand genome copy % hsa-mir-378b MI0014154 3p25.3 10371913 10371969 + No difference hsa-mir-885 MI0005560 3p25.3 10436173 10436246 - Deletion 25% hsa-mir-4270 MI0015878 3p25.1 15537746 15537815 - Amplification 80% hsa-mir-3134 MI0014155 3p25.1 15738805 15738878 - No difference hsa-mir-563 MI0003569 3p25.1 15915278 15915356 + No difference hsa-mir-3714 MI0016135 3p24.3 16974688 16974752 + No difference hsa-mir-4791 MI0017438 3p24.3 19356340 19356423 - No difference hsa-mir-3135a MI0014156 3p24.3 20179057 20179133 + No difference hsa-mir-4792 MI0017439 3p24.2 24562853 24562926 - Deletion 35% hsa-mir-4442 MI0016785 3p24.2 25706364 25706430 - No difference hsa-mir-466 MI0014157 3p23 31203196 31203279 - No difference hsa-mir-128-2 MI0000727 3p22.3 35785968 35786051 + Deletion 75% hsa-mir-26a-1 MI0000083 3p22.2 38010895 38010971 + Deletion 35% hsa-mir-138-1 MI0000476 3p21.32 44155704 44155802 + Deletion 25% hsa-mir-564 MI0003570 3p21.31 44903380 44903473 + Deletion 25% hsa-mir-1226 MI0006313 3p21.31 47891045 47891119 + No difference hsa-mir-4443 MI0016786 3p21.31 48238054 48238106 + No difference hsa-mir-2115 MI0010634 3p21.31 48357850 48357949 - No difference hsa-mir-711 MI0012488 3p21.31 48616335 48616410 - No difference hsa-mir-4793 MI0017440 3p21.31 48681627 48681713 - No difference hsa-mir-425 MI0001448 3p21.31 49057581 49057667 - Amplification 65% hsa-mir-191 MI0000465 3p21.31 49058051 49058142 - Amplification 65% hsa-mir-4271 MI0015879 3p21.31 49311553 49311619 + No difference hsa-mir-5193 MI0018172 3p21.31 49843570 49843678 - Deletion 35% hsa-mir-566 MI0003572 3p21.31 50210759 50210852 + No difference hsa-mir-4787 MI0017434 3p21.2 50712511 50712594 + No difference hsa-let-7g MI0000433 3p21.1 52302294 52302377 - Deletion 60% hsa-mir-135a-1 MI0000452 3p21.1 52328235 52328324 - Deletion 20% hsa-mir-3938 MI0016594 3p14.3 55886520 55886622 - Deletion 35% hsa-mir-4444-2 MI0019111 3p12.3 75263627 75263700 + Amplification 70% hsa-mir-1324 MI0006657 3p12.3 75679914 75680009 + No difference hsa-mir-4273 MI0015881 3p12.3 75787431 75787514 + Deletion 20% hsa-mir-3923 MI0016430 3p12.3 79557037 79557119 + No difference hsa-mir-5688 MI0019292 3p12.1 85434860 85434942 + Amplification 25%

Supplementary Table S2. Clinical significance of the expression of miR-128 in breast cancer patients.

Parameter n miR-128 expression (+), n (%) p value Age (years) ≤ 35 5 3 (60.0) 0.149 35-55 50 23 (46.0) > 55 30 8 (26.7) Tumor size (cm) ≤ 2 4 3 (75.0) 0.302 2-5 65 24 (36.9) > 5 16 7 (43.8) Lymph node metastasis Absent 30 21 (70.0) 0.020 Present 55 24 (43.6) Histology Ductual 80 20 (25) 0.206 Lobular 2 1 (50) Other types 3 2 (67) Grade I 3 1 (33.3) 0.810 II 54 23 (42.6) III 28 10 (35.7) Stage I -II 49 29 (59.2) 0.036 III-IV 36 13 (36.1) Estrogen receptor

－ 48 20 (41.7) 0.721

＋ 37 14 (37.8) Progesterone receptor

－ 50 18 (36.0) 0.368

＋ 35 16 (45.7) c-erbB-2 low 63 22 (34.9) 0.106 high 22 12 (54.5) Ki-67 + 19 10(52.6) 0.027 ++ 22 12 (54.5) +++ 31 10 (32.3) ++++ 13 2 (15.4)

Note: Estrogen and progesterone receptor, HER2/Neu and Ki67 data were obtained from patients’ pathology records.

Scoring stained sections (Supplement) The Ki67 labeling index (LI) was scored by counting 500 cells and determining the percentage of cells that stained positively for Ki67: score +, 0~25%; score ++, 26%~50%; score +++, 51%~75%; score ++++, > 75%. (Brown et al., 2002)

REFERENCE: Brown DC, Gatter KC. Ki67 : the immaculate deception. Histopathology 2002; 40:2-11. Supplementary Table S3. Invariable analysis of clinical outcome according to the expression of miR-128 in breast cancer patients (85 cases)

miR-128 expression 5-yr survival Positive Negative P Survival Time (months) (95% CL) 59.1(55.7-62.5) 52.9(48.8-57.2) 0.017 Overall survival Survival Rate (%) 76.5 52.0 Survival Time (months) (95% CL) 55.2(50.1-60.4) 44.8(38.7-50.9) 0.023 Relapse-free survival Survival Rate (%) 70.6 48.0

Supplementary Table S4. List of mRNAs predicted to be targeted by miR-128 by all the three programs: MiRanda, Pictar and TargetScan.

Target Gene Name ABCB9 ATP-binding cassette, sub-family B (MDR/TAP), member 9 ADCY2 adenylate cyclase 2 (brain) ADCY3 adenylate cyclase 3 ARID1B AT rich interactive domain 1B (SWI1-like) BAZ2B bromodomain adjacent to zinc finger domain, 2B BMI1 BMI1 polycomb ring finger oncogene BTG2 BTG family, member 2 C5orf13 chromosome 5 open reading frame 13 C9orf97 open reading frame 97 CA12 carbonic anhydrase XII CABP1 calcium binding protein 1 CASC3 cancer susceptibility candidate 3 CDH24 cadherin-like 24 CNR1 cannabinoid receptor 1 (brain) CORO1C coronin, actin binding protein, 1C CPEB3 cytoplasmic polyadenylation element binding protein 3 CRKL v-crk sarcoma virus CT10 oncogene homolog (avian)-like CSF1 colony stimulating factor 1 (macrophage) CTDSP2 CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase 2 DCX doublecortex; lissencephaly, X-linked (doublecortin) DIRAS2 DIRAS family, GTP-binding RAS-like 2 DTX1 deltex homolog 1 (Drosophila) E2F3 E2F transcription factor 3 ECE2 endothelin converting enzyme 2 ELMO1 engulfment and cell motility 1 EPHB2 EPH receptor B2 EVI5 ecotropic viral integration site 5 FBXO33 F-box protein 33 FLRT3 fibronectin leucine rich transmembrane protein 3 FOXP4 forkhead box P4 FOXQ1 forkhead box Q1 FXR2 fragile X mental retardation, autosomal homolog 2 GCC1 GRIP and coiled-coil domain containing 1 GNS glucosamine (N-acetyl)-6-sulfatase (Sanfilippo disease IIID) HAO1 hydroxyacid oxidase (glycolate oxidase) 1 HMGB3 high-mobility group box 3 HOXA13 homeobox A13 HOXB8 homeobox B8 ING5 inhibitor of growth family, member 5 ISL1 ISL LIM homeobox 1 ITPKC inositol 1,4,5-trisphosphate 3-kinase C KCNK10 potassium channel, subfamily K, member 10 KLF4 Kruppel-like factor 4 (gut) LIN28 lin-28 homolog (C. elegans) MAP2K4 mitogen-activated protein kinase kinase 4 MAP2K7 mitogen-activated protein kinase kinase 7 MAP4K5 mitogen-activated protein kinase kinase kinase kinase 5 MAPK14 mitogen-activated protein kinase 14 MGAT1 mannosyl (alpha-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase MOSPD3 motile sperm domain containing 3 MPP2 membrane protein, palmitoylated 2 (MAGUK p55 subfamily member 2) NANOG homeobox transcription factor Nanog NGFR nerve growth factor receptor (TNFR superfamily, member 16) NHS Nance-Horan syndrome (congenital cataracts and dental anomalies) NPTX1 neuronal pentraxin I NRBF2 nuclear receptor binding factor 2 NXF1 nuclear RNA export factor 1 NXT2 nuclear transport factor 2-like export factor 2 ORC5L origin recognition complex, subunit 5-like (yeast) PAIP2 poly(A) binding protein interacting protein 2 PDE3A phosphodiesterase 3A, cGMP-inhibited PDE7B phosphodiesterase 7B PHB prohibitin PLAGL2 pleiomorphic adenoma gene-like 2 PLK2 polo-like kinase 2 (Drosophila) PPP1CC protein phosphatase 1, catalytic subunit, gamma isoform PPP4C protein phosphatase 4 (formerly X), catalytic subunit PRDM16 PR domain containing 16 PTPN5 protein tyrosine phosphatase, non-receptor type 5 (striatum-enriched) PTPN9 protein tyrosine phosphatase, non-receptor type 9 RARA retinoic acid receptor, alpha RERE arginine-glutamic acid dipeptide (RE) repeats RNF38 ring finger protein 38 RPS6KA5 ribosomal protein S6 kinase, 90kDa, polypeptide 5 RYBP RING1 and YY1 binding protein SASH1 SAM and SH3 domain containing 1 SEC61A1 Sec61 alpha 1 subunit (S. cerevisiae) SH2D3C SH2 domain containing 3C SIRT1 sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) SLC35F3 solute carrier family 35, member F3 SLC39A13 solute carrier family 39 (zinc transporter), member 13 SLC6A1 solute carrier family 6 (neurotransmitter transporter, GABA), member 1 SNAI1 snail homolog 1 (Drosophila) SP1 Sp1 transcription factor SP2 Sp2 transcription factor SPATA2 spermatogenesis associated 2 STK24 serine/threonine kinase 24 (STE20 homolog, yeast) SYT1 synaptotagmin I TLK2 tousled-like kinase 2 TMEFF1 transmembrane protein with EGF-like and two follistatin-like domains 1 TMSB10 thymosin beta 10 TNPO3 transportin 3 UBE2E2 ubiquitin-conjugating enzyme E2E 2 (UBC4/5 homolog, yeast) ULK1 unc-51-like kinase 1 (C. elegans) WDTC1 WD and tetratricopeptide repeats 1 XPR1 xenotropic and polytropic retrovirus receptor YWHAB tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide ZNF24 zinc finger protein 24

Supplementary Table S5. qRT-PCR analysis of the effect of forced expression of miR-128 in MDA-MB-231 cells or depleted expression of miR-128 in MCF-10A cells on mRNA levels of several key functionally involved in oncogenicity and neoplastic progression.

Fold change with transfection Fold change with Functional gene by miR-128 mimics in transfection by miR-128 grouping Gene MDA-MB-231§ p-value ASO in MCF-10A& p-value CCND1 0.13 1.16E-04 3.08 6.83E-04 ATM 0.36 4.76E-04 4.76 4.25E-03 BRCA1 0.12 6.32E-04 1.73 1.64E-02

CCNE1 0.05 2.61E-03 6.73 2.54E-03

Cell cycle CDC25A 0.15 1.54E-03 1.20 6.72E-03 control and CDK2 0.45 1.45E-03 1.54 4.70E-02 DNA damage CDK4 0.53 1.62E-04 3.28 2.45E-04 repair CDKN1A 0.25 6.77E-04 2.64 1.06E-03

CDKN2A 9.43 3.87E-04 6.22 5.35E-04 CDKN1B 0.53 3.42E-03 3.95 4.73E-03 CHEK2 0.58 1.19E-02 1.59 2.32E-03 E2F1 0.04 1.31E-03 16.62 6.23E-05 MDM2 33.00 4.44E-04 0.34 5.02E-05 RB1 0.67 4.33E-04 1.52 7.17E-03 S100A4 0.76 2.96E-02 0.87 8.77E-02 TP53 36.08 4.51E-04 0.11 1.60E-04 APAF1 0.58 8.50E-03 0.20 1.19E-03 BCLAF1 1.93 1.15E-02 0.18 3.55E-04 BAK1 0.53 9.55E-04 0.22 9.89E-05

BAD 16.13 5.43E-03 0.15 3.70E-04 Apoptosis and BAX 0.31 4.50E-04 3.01 2.60E-03 cell senescence BCL2 0.10 5.91E-04 23.86 4.57E-04 BCL2L1 0.08 2.06E-03 3.29 3.49E-03 CFLAR 0.24 7.36E-04 0.67 7.18E-03 CASP7 4.93 1.67E-03 0.16 1.34E-05 GZMA 0.57 1.62E-02 8.50 7.45E-05 HTATIP2 0.19 4.30E-05 0.56 2.61E-03 TERT 0.22 1.99E-03 4.66 2.06E-03 TNFRSF1A 1.89 1.90E-02 0.19 2.95E-03 TNFRSF10B 2.43 6.88E-03 0.24 1.34E-03 TNFRSF25 8.77 6.28E-03 0.28 1.29E-03 AKT1 0.50 3.17E-03 1.25 2.79E-02 ERBB2 0.66 2.09E-03 1.24 4.56E-02 ETS2 0.26 1.65E-03 0.42 6.03E-03 FOS 0.30 2.80E-03 2.22 2.02E-04 JUN 0.56 1.69E-02 0.74 1.96E-02 Signal MAP2K1 0.58 2.87E-03 1.36 5.65E-03 transduction MYC 0.57 3.58E-03 1.50 1.26E-03 molecules and NFKB1 0.40 7.30E-02 1.43 5.20E-02 transcription NFKBIA 0.33 2.07E-03 1.65 1.65E-03 factors PIK3R1 0.70 5.23E-03 3.32 1.62E-03 RAF1 0.57 1.24E-02 1.59 3.84E-03 SNCG 0.63 5.62E-03 1.63 9.45E-03 STAT3 0.65 1.05E-03 1.48 2.09E-03 STAT5A 0.40 6.56E-05 1.99 6.40E-03 STAT5B 0.49 1.72E-03 1.65 3.80E-04 ANGPT1 0.33 5.77E-03 1.61 1.47E-02 ANGPT2 0.50 1.22E-02 1.92 1.08E-04 VEGF 0.29 1.34E-03 1.96 5.20E-03 COL18A1 0.42 6.86E-04 1.28 1.87E-05 Angiogenesis IL8 0.07 2.09E-04 5.06 3.60E-04 TEK 0.56 1.30E-03 3.80 2.49E-05 TGFB1 0.51 3.66E-03 0.87 1.35E-01 TGBS1 0.33 3.42E-03 0.79 3.96E-02 TNF 0.22 2.61E-03 1.79 1.18E-04 MET 0.14 6.78E-04 4.13 1.49E-03 MMP1 0.05 2.76E-03 8.83 8.84E-04 MMP2 0.07 2.27E-03 6.36 4.61E-04 MMP9 0.13 1.38E-03 12.55 1.60E-04 MTA1 0.26 2.26E-03 1.49 2.08E-02 MTA2 0.33 3.67E-03 1.58 4.49E-04 Invasion and NME1 0.63 1.49E-02 1.31 3.13E-03 metastasis PLAU 0.16 2.54E-03 1.98 1.07E-02 PLAUR 0.52 2.16E-03 1.65 1.21E-03 SERPINB5 0.12 4.82E-03 5.22 1.21E-04 SERPINE1 0.03 6.18E-05 2.94 1.22E-04 TIMP1 0.57 1.08E-02 1.71 1.53E-02 TIMP3 0.34 1.90E-03 1.89 5.72E-04 TWIST1 1.43 1.82E-01 1.24 3.07E-01 VIM 0.80 1.18E-01 0.93 1.54E-03 FN1 0.77 8.20E-03 1.02 3.18E-02 OCLN 0.74 4.65E-02 1.07 2.84E-01 Cell remodeling CTNNA1 0.75 1.03E-02 0.88 2.27E-03 CTNNB1 0.74 1.85E-02 0.95 6.18E-03 CTNND1 0.43 1.97E-04 3.99 1.59E-02 CDH1 16.56 7.66E-03 0.25 8.79E-04 CD24 0.82 8.94E-03 0.94 3.65E-02 CD44 0.95 1.67E-01 1.35 2.83E-01 FOXC2 1.74 2.05E-01 4.01 2.04E-01

ZEB1 0.70 2.65E-03 1.67 3.66E-04

ZEB2 1.15 4.19E-01 2.45 2.75E-02 CDH2 0.18 1.02E-03 1.47 9.26E-04 CSF1 0.76 1.05E-01 2.07 1.98E-02 NOTCH1 0.99 1.92E-01 3.66 1.06E-01

IGF1 1.83 1.71E-01 0.98 1.98E-02

Stem cell KLF4 0.78 2.28E-02 1.45 8.63E-02 factors SRC 0.81 8.30E-03 0.48 7.03E-04 SNAIL 0.74 2.17E-01 1.89 2.04E-01 SNAIL2 0.73 4.69E-04 2.96 1.75E-02 EGFR 0.78 8.61E-03 0.98 8.63E-02 NCAM1 4.42 3.73E-03 0.73 4.98E-03 ALDH1 0.57 1.10E-02 2.50 7.77E-04 WNT5A 1.09 3.95E-01 1.78 4.05E-02 WNT5B 0.74 1.03E-01 1.24 2.69E-02 BMI1 0.57 1.31E-02 3.26 1.54E-03 LIN28A 1.29 5.62E-02 1.02 3.18E-02 NANOG 1.04 3.14E-01 1.07 2.84E-01 SOX2 0.88 7.61E-03 4.56 2.27E-03 POU5F1 1.48 2.49E-01 0.95 1.76E-02 SALL4 1.45 8.64E-02 3.99 2.15E-02

Footnote: §Results are presented as a fold change in mRNA levels in MDA-MB-231 cells transfected with miR-128 mimics relative to

MDA-MB-231 cells transfected with control oligonucleotide.

&Results are presented as a fold change in mRNA levels in MCF-7 cells transfected with miR-128 ASO relative to MCF-10A cells transfected with scrambled sequence oligo nucleotide.

# Each change in gene expression is expressed as fold change, respectively.

Note: Positive and negative fold change indicates an increase or decrease in mRNA levels.

Supplementary Table S6. Sequences of the oligonucleotides for miRNAs, siRNAs, construct-making and ChIP assays.

miRNA and siRNA Duplexes Sense Strand (5'-3') Antisense Strand (5'-3') hsa-miR-128 mimic UCACAGUGAACCGGUCUCUUU AGAGACCGGUUCACUGUGAUU SNAIL siRNA -1 AGUUCUGGGAGACACAUCGGUCTT GACCGAUGUGUCUCCCAGAACUTT SNAIL siRNA -2 GCGAGCUGCAGGACUCUAATT UUAGAGUCCUGCAGCUCGCTT Negative Control (NC) UUCUCCGAACGUGUCACGUTT ACGUGACACGUUCGGAGAATT hsa-miR-128 inhibitor AAAGAGACCGGUUCACUGUGA MicroRNA inhibitor NC CAGUACUUUUGUGUAGUACAA Primers for plasmid construction Sense Strand (5'-3') Antisense Strand (5'-3') CGCGGATCCATGTTAAACAGTCTCCA CCGGAATTCAGCAGCAAGGAGCACGTGCTC pri-miR-128-2 cloning primer TAA TT CCGCTCGAGTACCTGAGACTGTTAAG BMI1 3’UTR cloning primer GA ATAAGAATGCGGCCGCTTGGCAAACATTGGT CCGCTCGAGAGGGAATTCTAAGCTGG ATAAGAATGCGGCCGCTGGGGAGAGGCTGG CSF1 3’UTR cloning primer A AGA CCGCTCGAGATCCCAGACAGTGGATA ATAAGAATGCGGCCGCCAGATAAAATATTAT KLF4 3’UTR cloning primer TGA AGGT LIN28A 3’UTR cloning primer CCGCTCGAGCTATCAGGAAGTTTTGA ATAAGAATGCGGCCGCGGAAAGGAGAAGGG GGAGCAG AAGGGA CCGCTCGAGAGATGAGTGAAACTGAT ATAAGAATGCGGCCGCATGTTTAAGCTGTAT NANOG 3’UTR cloning primer AT ATT TTATCTGTTTAAACCCCTCGAGGCTCC TCAGTGGCGGCCGCATATATAAATTAACTGC SNAIL 3’UTR cloning primer CTCTT TTTAT GAATAATGCATTCTATGTAGCCATGAT GGCTAAATATGCAAGAAATCGTTATCATGGC BMI1 3’UTR Mutation primer AACGATTTCTTGCATATTTAGCC TACATAGAATGCATTATTC CATGAAGGAAGCCATTGACACTGTAC GCAGGCAGGTACAGTGTCAATGGCTTCCTTC CSF1 3’UTR Mutation primer CTGCCTGC ATG TTTTATGCAGACAGTCTGTTATGGTTT ACAAATTATTGCACATCTGAAACCATAACAGA KLF4 3’UTR Mutation primer CAGATGTGCAATAATTTGT CTGTCTGCATAAAA LIN28A 3’UTR Site 1 Mutation AAGGCCCTCATTTCCTGTTCTCAGGTA GCTCATGTACCTGAGAACAGGAAATGAGGG primer CATGAGC CCTT LIN28A 3’UTR Site 2 Mutation TTTTTTTTTAAAATGGAGTCTCACCCA CTGCACTCCAGCCTGGGTGAGACTCCATTTT primer GGCTGGAGTGCAG AAAAAAAAA TTAGTAGAGACGGGGTTTTAGCCAGG GAGACCATCCTGGCTAAAACCCCGTCTCTAC NANOG 3’UTR Mutation primer ATGGTCTC TAA TAACAATGTCTGAAAAGGGGTAATGG GACAAGTGACAGCCATTACCCCTTTTCAGAC SNAIL 3’UTR Mutation primer CTGTCACTTGTC ATTGTTA pri-miR-128-2 promoter cloning CTAGCTAGCCAATGACTTAGTTGCCA CCGCTCGAGGTGGCTGCCGGGCTCT primer GATACTGA pri-miR-128-2 promoter Ebox1 GGGGGTACCTGTGTTCCTTTTTCTGC ATTCTGCTGCAGAAAAAGGAACACAGGTACC Mutation primer AGCAGAAT CCC pri-miR-128-2 promoter Ebox2 TCACTTTCATGATGGCCTGCCCAGAG CGGGCTCTGGGCAGGCCATCATGAAAGTGA Mutation primer CCCG

miR-128 knock down Inserted Sequence (5'-3') AAAGAGACCGCACACTGTGACGATAAAGAGACCGCACACTGTGAACCGGTAAAGAGAC CGCACACTGTGATCACAAAGAGACCGCACACTGTGACCCGGTGCATGACTAAGCTAGA miR-128 Sponge TAAAAAGAGACCGCACACTGTGACGATAAAGAGACCGCACACTGTGAACCGGTAAAGA GACCGCACACTGTGATCACAAAGAGACCGCACACTGTGA GGAGCTCCACCGCGGTGGCATCGATGGAGCTCCACCGCGGTGGCATACCGGTGGAGC TCCACCGCGGTGGCATTCACGGAGCTCCACCGCGGTGGCATCCCGGTGCATGACTAA GCTAGATAAGGAGCTCCACCGCGGTGGCATCGATGGAGCTCCACCGCGGTGGCATAC Sponge Control CGGTGGAGCTCCACCGCGGTGGCATTCAC GGAGCTCCACCGCGGTGGCAT Primers for ChIP assay Sense Strand (5'-3') Antisense Strand (5'-3') GTGGCTTGACTAGGGCTACACTTACATGCCTGGAACTGGAGGGTAACCAGTCAATTGG Proximal promoter containing GGGTACCTGTGTTCCCCACATGGCCTTTTTCTGCAGCAGAATAGTCTAGACTTCTTTATC EBox1 Site amplified by PCR in TCTTGGCTGGGTTCCCCGCCTACAGACGTGGAAGCTGCAAGTCTTC ChIP assay (164 bp) (-1071 to – 907 from Transcription Start Site) Primers for EBox1 promoter PCR GTGGCTTGACTAGGGCTACACTTAC GAAGACTTGCAGCTTCCACGTCTGT CTATTGACAATCCAGCGTGTCTCGGTGGAACTCTGACTCCATGGTTCACTTTCATGATG Proximal promoter containing GCCACATGCCTCCTGCCCAGAGCCCGGCAGCCACTGTGCAGTGGGAAGGGGGGCCGA EBox2 Site amplified by PCR in TACACTGTACGAGAGTGAGTAGCAGGTCTCACAGTGAACCGGTCTCTTTCCCTACTGTG ChIP assay (205 bp) TCACACTCCTAATGGAATGCCGTTATCCAA (-93 to +112 from Transcription Start Site) Primers for EBox1 promoter PCR CTATTGACAATCCAGCGTGTCTCGG TTGGATAACGGCATTCCATTAGGAG Distal promoter without EBox Site ATGAGCTTACATTTAAGCAAGACAGTCTTTTCTAAAGGAACAAAACGCTATTTCCTAAAA amplified by PCR in ChIP assay GACATGTAAATATAAATGCTGACAAATAAATTAGATGAAAGTTGTTCCTATTTTTAATATT (170 bp) GGGAGGCATCTGATGCATAATGGTAGTCATCTTTAATACCACCAAAGTT (-2286 to – 2116 from Transcription Start Site) Primers for distal promoter PCR ATGAGCTTACATTTAAGCAAGACAG AACTTTGGTGGTATTAAAGATGACT Supplementary Table S7. Sequence of the oligonucleotides for real-time PCR experiments.

miRNA genomic Amplicon real-time PCR Sense Strand (5'-3') Antisense Strand (5'-3') (bp)

hsa-mir-378b GCAAGTTCTTTCATTTTCTGTCTCA AGTCCAGTGCTCTTTCCACTAGCCT 124

hsa-mir-885 GAGCACGAGGCAGTAGGCAAAGTGT GAGGCAGCGGGGTGTAGTGGATAGA 195

hsa-mir-4270 CCTTTCTTCCTGGAAATTGGAGACC AGTCAGGGGAGGGCAGAAATAGATG 172

hsa-mir-3134 AATGATAGAATGGACTTTGGGGACT ATTGATGATTTCTGAGATTTTGGTG 168

hsa-mir-563 GACATACGTTTCCCTGGTAGCCAATA CTTCCCAACCTTGACATCTAATCCA 96

hsa-mir-3714 GTTGATTCCAGCACCACTTTGTGAG TGCTCCTCTTTTGCAGTCCTTCACT 153

hsa-mir-4791 CTGAATAGCTGGATAGCTTTTCTAA TAAAGCAATACCACAACAACAGTCT 155

hsa-mir-3135a AGCACATAGTGGGCTAGGAGCTTGG ACTTGGGAGGCTGAGGTGGGAGAAT 192

hsa-mir-4792 TGTGAAGTTCGTGAACAAGCATCTA CTGGCTACACTGTCCTGGGGAAAAC 109

hsa-mir-4442 CGCAGAGGTGCCTTGTCCTTCTCAC GCGGCGGCGGCTCTGTTTATTGTCC 168

hsa-mir-466 AGACCAGACCTAAAGGAAGACATAA ATGGCACCTAGATCAAGATACAGAA 144

hsa-mir-128-2 AGAGCAGCACGAACCCGACAG AGAAGGCAGAGTCTCCCCGTCA 133

hsa-mir-26a-1 CCTGCCCACTGCTGACCCATTCTTG TTGGCTCCTGTGGCTTCATTCCCTC 128 hsa-mir-138-1 GGGATGGGGAAGTTCACAAAAGGCACA CAGCCAGAAGTGAGAACCGGGAAGC 110 CGGCCTAACCTGTAGTAGGTTTGTG

hsa-mir-564 GATGGAGACGGCTAAGCCGCGAGAA CTCT 123 GGAGGAAAAGACGGGTGGGGCTGA

hsa-mir-1226 GAGCTGGTGAAGGGCGTGCTGATGG G 142

hsa-mir-4443 AATTGTTCCTGGATTCCTTCCTGTC CTTCCCCATACTGCACTTTGCTTAA 99

hsa-mir-2115 TCCTCATACTGCTTCTAGCCTCCAT CTTTCAGCATTTTGACTGTCATCCC 107

hsa-mir-711 CCTCCCAAAGGCAAGGCTGAACCGAC CGGGGCTGCGTAAGCTCCAACCAGA 88

hsa-mir-4793 CCCCTTCCTCCAGCCAGCCAACTCA GTTTCTCCTCGCTGCCCGCACATCC 92

hsa-mir-425 CAGGGAAACCCAGGGGCAGGAAAAG GCACCCGAGAAGCCATCGGGAATGT 123

hsa-mir-191 CATCACCTCCAGCCTGAGGGCGCAACT CAGCGGGCAACGGAATCCCAAAAGC 190

hsa-mir-4271 CATGTGAAGGACCTATCTTCCCAAGG AGCCAAGAGGTCACAAAGGATCTGC 91

hsa-mir-5193 CACTTCAGGTGATGGAACTGGGATG GGAAAGGCTGCTGGTAACTGGGATG 93

hsa-mir-566 CTGCCTACCTGTGCCACTTTGTCCT GTCTTAAACCTCCAGCTCCCCTTCC 92

hsa-mir-4787 GCCGGGCAGTCCAATAGCTTCTCGC CGTGCCGCCGCTTGCTTCTTCACAG 225 hsa-let-7g GAGTTCCTCCAGCGCTCCGT GATGAGCAGGGTGACGCCAT 178

hsa-mir-135a-1 TGGTGGGTCCAGCCAGTGATGAGGT CGGAGGGTTCTGACACTGAGCAAGG 185

hsa-mir-3938 GGTAAGATAAATATGGCCCAGAGGG TAGGAGAACTTGCTGTTGTGCCTCT 93

hsa-mir-4444-2 GAATCTGACTCAAAATATCAGGGAA AAATAAATGACTTGGCAAGGTTGTA 157

hsa-mir-1324 TCAGGGCAAGAACCCAGAGCAGATG AGAGGGAGATGTTCAGCCACCAAGC 83 hsa-mir-4273 GCCTTGACTTATGGCTAAATGCTTC ATCACAGAACTCACTCAGGGGAAAA 159

hsa-mir-3923 GGGCTCACTCTACTATTCTCAGCAA TTCTCATCGTTCAACTCCCACTTAT 104

hsa-mir-5688 ATCCTTGTTTTATGAGGTTGGGCTAT ACCTGCCAAAACTCAATTCTTTCCT 85 β-ACTIN Genomic qRT-PCR TGACTTAGTTGCGTTACACCCTT CACCTTCACCGTTCCAGTTTT 156 Amplicon Gene Sense Strand (5'-3') Antisense Strand (5'-3') (bp) GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCAC miR-128 Stem-loop RT-PCR Primer TGGATACGACAAAGAG Mature miR-128 real-time Primer gCCgCTCACAGTGAACCGGT gTgCAgggTCCgAggT 66 ARPP21 CCCATCTGGTCAGTACCCTACC CACGCTTTGCACCGGAGTT 225 PRI-MIR-128-2 AGAGCAGCACGAACCCGACAG AGAAGGCAGAGTCTCCCCGTCA 133 PRE-β-ACTIN GACTCTCTTCTCTGACCTGAG ACACGAGCCAGTGTTAGTACC 146 BMI1 AAATGCTGGAGAACTGGAAAG CTGTGGATGAGGAGACTGC 124 CSF1 GCAGCGGCTGATTGACAGT CAGCTGCACAATGGCGAT 185 KLF4 ACATGGCTGTCAGCGACGCG GCCAGCGGTTATTCGGGGCAC 108 LIN28A TTCGGCTTCCTGTCCATGAC TGACTCAAGGCCTTTGGAAG 123 NANOG CAACCAGACCCAGAACATCC TTCCAAAGCAGCCTCCAAG 185 SNAIL TGCGCTACTGCTGCGCGAAT GGGCTGCTGGAAGGTAAACTCTGGA 147 CD44 CAGGGACAGCTGCAGCCTCA ACCTCGTCCCATGGGGTGTG 122 CD24 CCAACTAATGCCACCACCA GACGTTTCTTGGCCTGAGTC 118 CD133 GGAATCCTTTCCATTACGGCG AGACCCTGGCTCGTGAATTA 231

Supplementary Table S8. List of tested by antibodies and characteristics of the corresponding antibodies used. Protein Assay Antibody Origin Dilution Incubation period BMI1 WB rpab #NB110-40823,Novus 1:1000 overnight BMI1 IHC rpab #NB110-40823,Novus 1:50 overnight CSF1 WB rpab #AJ1466a,Abgent 1:500 overnight CSF1 IHC rpab #AJ1466a,Abgent 1:100 overnight KLF4 WB mmab #AP2725a,Abgent 1:500 overnight KLF4 IHC mmab #AP2725a,Abgent 1:50 overnight LIN28A WB rpab #3978,Cell Signaling 1:1000 overnight LIN28A IHC rpab #3978,Cell Signaling 1:50 overnight NANOG WB rpab #14295-1-AP,Proteintech 1:1500 overnight NANOG IHC rpab #14295-1-AP,Proteintech 1:50 overnight SNAIL WB rpab #sc-28199,Santa Cruz 1:1000 overnight SNAIL IHC rpab #sc-28199,Santa Cruz 1:100 overnight SNAIL ChIP rpab #sc-28199,Santa Cruz 2 ug overnight Phospho-AKT , Ser473 WB rpab #9271,Cell Signaling 1:1000 overnight Phospho-AKT , Ser473 IHC rpab #3787,Cell Signaling 1:50 overnight AKT WB rpab #9272,Cell Signaling 1:1000 overnight AKT IHC rpab #9272,Cell Signaling 1:50 overnight Phospho-STAT3 ,Y705 WB rmab #Ab76315,Abcam 1:5000 overnight Phospho-STAT3 ,Y705 IHC rmab #Ab76315,Abcam 1:100 overnight STAT3 WB rpab #P30007,Abmart 1:1000 overnight STAT3 IHC rpab #P30007,Abmart 1:50 overnight FN1 WB mmab # 610077,BD 1:5000 overnight Vimentin WB mmab # 550513,BD 1:5000 overnight E-Cadherin WB mmab # 610181,BD 1:5000 overnight plakoglobin WB mmab #sc-8415,Santa Cruz 1:1000 overnight FITC-CD44 IF mmab # 553133,BD 1:50 1 hour PE-CD24 IF mmab # 555428,BD 1:100 1 hour β-ACTIN WB mmab #M20010,Abmart 1:5000 1 hour

Abbreviations: WB, Western blot; ChIP, chromatin immunoprecipitation; IHC, immunohistochemistry;

IF, immunofluorescence; mmab, mouse monoclonal antibody; rpab, rabbit polyclonal antibody.