Background
Methods
Patients recruitment
Lymphocyte and miRNA isolation
The quality control of the miRNAs
Microarray trial protocol
Data analysis
Bioinformatic analysis
Comparison groups
Group 1 | Group 2 | Group 3 | Group 4 | |
---|---|---|---|---|
Case | BR1639 | BR1639 BR1447 BR1547 BR2030 BR1546 BR1861 | BR1639 | BR1639 BR1447 |
Control | BR1447 | BR1850 BR2028 | BR1447 BR1547 BR2030 BR1546 BR1861 | BR1547 BR2030 BR1546 BR1861 BR1850 BR2028 |
Results
miRNAs | Fold change (FC) values | Sequence of miRNA | miRNAStatus | Target genes |
---|---|---|---|---|
miR-1273 g-3p | 3,57 | ACCACUGCACUCCAGCCUGAG | Upregulated | ZNF138, TMEM239, BMP3 |
miR-1305 | 2,05 | UUUUCAACUCUAAUGGGAGAGA | Upregulated | PTPN4, PRKAA1, PAPD7, FRAT2, DEPDC1, FBXO41 |
miR-197-3p | 2,7 | UUCACCACCUUCUCCACCCAGC | Upregulated | CD82, PMAIP1, MTHFD1, CHECK1, AGO1, CASP10 |
miR-3651 | 2,17 | CAUAGCCCGGUCGCUGGUACAUGA | Upregulated | RACGAP1, OLA1, TEX261, PTGS1, NFIC, ZNF200 |
miR-6131 | 2,22 | GGCUGGUCAGAUGGGAGUG | Upregulated | PAGR1, IGF2BP1, CACNG8 |
miR-92a-3p | 2,09 | UAUUGCACUUGUCCCGGCCUGU | Upregulated | STAT3, PTEN, ATM, NOTCH2, CDH1, NFKB1 |
let-7i-5p | −2,45 | UGAGGUAGUAGUUUGUGCUGUU | Downregulated | TLR4, BMP4, EIF2C1, NEUROG1, SOCS1, IGF1 |
miR-125a-5p | -5,96 | UCCCUGAGACCCUUUAACCUGUGA | Downregulated | ERBB3, CDKN1A, TP53, ERBB2, EGFR, STAT3,MYC, VEGFA |
miR-15b-5p | -3,61 | UAGCAGCACAUCAUGGUUUACA | Downregulated | BCL2, VEGFA, CCND1, CCNE1, CDK1, CDK4, CDK6, E2F3, MAPK1 |
miR-22-3p | -8,92 | AAGCUGCCAGUUGAAGAACUGU | Downregulated | CDKN1A, WNT1, ERBB3, MYCBP, HMGB1, E2F2, PTEN, POTED, SOD2, |
miR-3135b | -4,38 | GGCUGGAGCGAGUGCAGUGGUG | Downregulated | BIRC5, ABL2, MAPK1, MYCN |
miR-320d | -2,01 | AAAAGCUGGGUUGAGAGGA | Downregulated | DCTN5, SYNCRIP, FBXO28 |
miR-342-3p | -2,36 | UCUCACACAGAAAUCGCACCCGU | Downregulated | GEMIN4, DNMT1, ID4, SREBF1,SREBF2, BMP7 |
miR-4430 | -2,01 | AGGCUGGAGUGAGCGGAG | Downregulated | ZNF485,ABL2, MAPK1, MSH5, PTEN |
miR-451a | -12,89 | AAACCGUUACCAUUACUGAGUU | Downregulated | CPNE3, RAB5A, IL6R, AKT1, MMP2 |
miR-664b-5p | -3,21 | UGGGCUAAGGGAGAUGAUUGGGUA | Downregulated | CD55,MSN, RHOBTB3, PLAG1 |
miR-766-3p | -2,02 | ACUCCAGCCCCACAGCCUCAGC | Downregulated | COX1, MAPK1, NF2, RAD51, STK4, STK24, VEGFC |
miRNAs | Fold change (FC) values | Sequence of miRNA | miRNAStatus | Target genes |
---|---|---|---|---|
miR-4449 | 2,56 | CGUCCCGGGGCUGCGCGAGGCA | Upregulated | ZFHX3 |
miR-4653-3p | 2,92 | UGGAGUUAAGGGUUGCUUGGAGA | Upregulated | ATG2A, CREBL2, MAT2A, FRS2, TMED4, UBN2 |
miR-486-5p | 3,34 | UCCUGUACUGAGCUGCCCCGAG | Upregulated | OLFM4,CD40,ARHGAP5, IGF1R, DOCK3, CADM1 |
miR-5739 | 2,03 | GCGGAGAGAGAAUGGGGAGC | Upregulated | DLX6,CD207,CHIC1,PPL2A, PLXDC1 |
miR-6165 | 2,24 | CAGCAGGAGGUGAGGGGAG | Upregulated | PER1,TFAP2A,FADS1, AMER1,LUZP1, COX6B1 |
miR-874-3p | 2,08 | CUGCCCUGGCCCGAGGGACCGA | Upregulated | HDAC1, AQP3, STAT3, CDK9 |
miR-126-3p | −24,03 | UCGUACCGUGAGUAAUAAUGCG | Downregulated | TOM1, CRK, VEGFA, SOX2, TWF1, PITPNC1, IGFBP2, KRAS |
miR-320a | −2,55 | AAAAGCUGGGUUGAGAGGGCGA | Downregulated | MCL1, BANP, ITGB3, BMI1, NRP1, NFATC3, TRPC5 |
miR-320b | −2,45 | AAAAGCUGGGUUGAGAGGGCAA | Downregulated | CDK6,DCTN5,SYNCRIP,ARF1, BCL9L, ZNF600 |
miR-320c | −2,26 | AAAAGCUGGGUUGAGAGGGU | Downregulated | SYNCRIP,FBXO28,SMARCC, NPM3 |
miR-320d | −2,39 | AAAAGCUGGGUUGAGAGGA | Downregulated | DCTN5, SYNCRIP, FBXO28 |
miR-320e | −2,42 | AAAGCUGGGUUGAGAAGG | Downregulated | DCTN5, NPM3, ZNF275, DDX19A, NCAPD2, TXNL1 |
miR-324-3p | −2,98 | ACUGCCCCAGGUGCUGCUGG | Downregulated | WNT9B, CREBBP, DVL2, WNT2B |
miR-3656 | −2,16 | GGCGGGUGCGGGGGUGG | Downregulated | MRPL12, LSP1, MNT, PRDM2, ZNF770, CECR1 |
miR-4284 | −2,96 | GGGCUCACAUCACCCCAU | Downregulated | BCL2L11,RBBP5,HNRNPA1, ZNF264, TRIB3, CRTAP |
miR-4428 | −6,05 | CAAGGAGACGGGAACAUGGAGC | Downregulated | MSL1,MAPRE3,MYH14,CASP2, CCND2, CDK14,TP63 |
miR − 4516 | -4,34 | GGGAGAAGGGUCGGGGC | Downregulated | STAT3,M6PR,GPR137C,CCND2, CCNT1, CDKN1A, SCOC, TP53 |
miR-4741 | −3,65 | CGGGCUGUCCGGAGGGGUCGGCU | Downregulated | DDX39B,MAPK1, ZBTB39, HMGA1, |
miR-484 | −2,97 | UCAGGCUCAGUCCCCUCCCGAU | Downregulated | FIS1, PAGR1, ZEB1, SLC11A2, SMAD2, ANAPC7, TBRG1 |
miR-564 | −2,45 | AGGCACGGUGUCAGCAGGC | Downregulated | GID4, CNBP, E2F3, RCAN3, AKT2, APPL1, SLC1A2, GPR155 |
miR − 6089 | -6,03 | GGAGGCCGGGGUGGGGCGGGGCGG | Downregulated | NKX2, TPT1, KCTD5, BBX, SGCD, CDH7, CCNB1, |
miR-6869 − 5p | -5,38 | GUGAGUAGUGGCGCGCGGCGGC | Downregulated | TUBB2A,MAPK1,NRBF2, WEE1,HMGA2, MAPK1, STAG2 |
miR-6891-5p | −2,23 | UAAGGAGGGGGAUGAGGGG | Downregulated | CHD4, CD207, DDX6, CHRDL1, CCND2, TP63 |
miR-7107-5p | −3,43 | UCGGCCUGGGGAGGAGGAAGGG | Downregulated | VAV3, CASP16, CCND1, CASP16, MAPK14, |
miR-7847 − 3p | -3,1 | CGUGGAGGACGAGGAGGAGGC | Downregulated | HAVCR1, POTED, DNAJC10, SOD2, M6PR, CDK19 |
miRNAs | Fold change (FC) values | Sequence of miRNA | miRNAStatus | Target genes |
---|---|---|---|---|
miR-1260a | 11,7 | AUCCCACCUCUGCCACCA | Upregulated | PSAT1,UNC13A, RPS27, BRD7 |
miR-1260b | 6,65 | AUCCCACCACUGCCACCAU | Upregulated | SFRP1, DKK2, SMAD4, PSAT1,UNC13A, RPS27 |
miR-16 − 5p | 11,5 | UAGCAGCACGUAAAUAUUGGCG | Upregulated | CCNE1, ARL2, BCL2, HMGA1, CDK6, CCND1, VEGFA, RECK, PRDM4 |
miR-17-5p | 23,2 | CAAAGUGCUUACAGUGCAGGUAG | Upregulated | TGFBR2, PTEN, CDKN1A, BCL2L11, E2F1,TP53,STAT3 |
miR-181b-5p | 2,85 | AACAUUCAUUGCUGUCGGUGGGU | Upregulated | TCL1A, TIMP3, PLAG1, BCL2,RNF2,VSNL1, ATM |
miR-26b-5p | 12,5 | UUCAAGUAAUUCAGGAUAGGU | Upregulated | PTGS2, EPHA2, CHORDC1, EZH2, CCNE1,ABCA1, GATA4 |
miR-4281 | 2,75 | GGGUCCCGGGGAGGGGGG | Upregulated | NCDN, CDKN1A, BCL3 |
miR-4286 | 25,6 | ACCCCACUCCUGGUACC | Upregulated | LDLR, ZNF354B, NSD1, RABGAP1, TAOK1, MKNK2 |
miR-5100 | 17,1 | UUCAGAUCCCAGCGGUGCCUCU | Upregulated | COX10, DEK, KCNN3, RAB11FIP1, DYNLT1, NOTCH2 |
miR-6840-3p | 2,51 | GCCCAGGACUUUGUGCGGGGUG | Upregulated | SLFN12L, CTC1, GXYLT2, GDE1,FADS1,PER1, ATG9A |
miR-7114-5p | 2,89 | UCUGUGGAGUGGGGUGCCUGU | Upregulated | M6PR, HNRNPUL1, SHMT1, ZNF529,ACVR2B, PAICS, TAF8 |
miR-7975 | 6,94 | AUCCUAGUCACGGCACCA | Upregulated | KBTBD8,GULP1, CASZ1, RAD51 |
miR-7977 | 16,1 | UUCCCAGCCAACGCACCA | Upregulated | HSPA1B, ZNF703, TMEM185B, SF3B3,COX6B1, CCDC9, CDH7 |
miR-1225-5p | -5,12 | GUGGGUACGGCCCAGUGGGGGG | Downregulated | ORC4, ODF2L, MTRNR2L7, PSMG2, MTRNR2L3 |
miR-142-3p | −29,06 | UGUAGUGUUUCCUACUUUAUGGA | Downregulated | ARNTL,TGFBR1, RAC1, ROCK2,, CCNT2, TAB2, PTPN23, |
miR-26a-5p | −7,88 | UUCAAGUAAUCCAGGAUAGGCU | Downregulated | EZH2,RB1,ADAM17, HMGA2,CCND2, CPEB3, DNMT3B |
miR-2861 | −4,57 | GGGGCCUGGCGGUGGGCGG | Downregulated | LY6E,CCDC64, CCND1, DARS2, APAF1 |
miR-29a-3p | −8,67 | UAGCACCAUCUGAAAUCGGUUA | Downregulated | MCL1,CDK6,SPARC, DNMT3A,DNMT3B, COL4A1 |
miR-30d-5p | −4,45 | UGUAAACAUCCCCGACUGGAAG | Downregulated | GNAI2, TP53, CASP3, SNAI1, EZH2, BCL9, NOTCH1, SMAD1 |
miR-3196 | −4,55 | CGGGGCGGCAGGGGCCUC | Downregulated | POU3F3,TULP1, H2AFX,PCGF3, CASP16,ATG2A, CCDC64 |
miR − 342-3p | -3,7 | UCUCACACAGAAAUCGCACCCGU | Downregulated | GEMIN4, DNMT1, ID4, SREBF1,SREBF2, BMP7, RMND5A |
miR-3665 | −2,75 | AGCAGGUGCGGGGCGGCG | Downregulated | RAB5C,DNAJC15, ZNF85, MRPL17, ELF4, ENPP6, CASP2 |
miR-3960 | −4,64 | GGCGGCGGCGGAGGCGGGGG | Downregulated | POU3F3,PRX,PIAS4, PEG10 |
miR-4466 | −2,9 | GGGUGCGGGCCGGCGGGG | Downregulated | NAGK,NFX1,F2R, DDA1, AACS |
miR-4530 | −3,06 | CCCAGCAGGACGGGAGCG | Downregulated | HES4, DMPK, CALM2, GPRC5A,ATAT1, CALM2, PTCH1 |
miR-4687-3p | −2,01 | UGGCUGUUGGAGGGGGCAGGC | Downregulated | ZBTB39, SLC37A4, ADAP1, FHL2, BARHL1, AKAP6, |
miR-4787-5p | −7,7 | GCGGGGGUGGCGGCGGCAUCCC | Downregulated | STMN3,VPS51, MYADM,CYP2B6, SNX19, PER3, FN3K |
miR-494-3p | −8,32 | UGAAACAUACACGGGAAACCUC | Downregulated | PTEN,CDK6,MYC, BCL2L11,BCL2, ATXN1, MAPK1, MDM4 |
miR-5001-5p | −4,8 | AGGGCUGGACUCAGCGGCGGAGCU | Downregulated | SPTBN2,RAD54L2, NF2,CDK2, COX6B1, MAP3K9 |
miR-5006-5p | −3,1 | UUGCCAGGGCAGGAGGUGGAA | Downregulated | KLHL15,ZNF354B, GIGYF1,ACTG1, RRP7A, PRPF40A |
miR − 5787 | -5,16 | GGGCUGGGGCGCGGGGAGGU | Downregulated | ELF5,RAB5B,ORC4, CD4,MSH5,NF2, PARP2, PTEN |
miR-6068 | −3,75 | CCUGCGAGUCUCCGGCGGUGG | Downregulated | BTG1,DUSP3, TMEM170A |
miR-6087 | −3,23 | UGAGGCGGGGGGGCGAGC | Downregulated | GSG2, FADS1, CNBP, AGO3, CSTF2, HOXD3, BAG5 |
miR-6088 | −3,21 | AGAGAUGAAGCGGGGGGGCG | Downregulated | USP42,SECISBP2L, RAB22A,CASP5, MAPK1 |
miR-6090 | −3,83 | GGGGAGCGAGGGGCGGGGC | Downregulated | AVL9, QSOX2, GNAI2, FAM43A,E2F6, MAP3K2 |
miR-6124 | −3,3 | GGGAAAAGGAAGGGGGAGGA | Downregulated | DNAJB9, BCAN, E2F3, RAD21,BCL2L12, CASP3, CDKN1A |
miR-6125 | −4,6 | GCGGAAGGCGGAGCGGCGGA | Downregulated | HAVCR1,AEN, ZMYM1, BICD2, BCR, CASP16, |
miR-638 | −4,7 | AGGGAUCGCGGGCGGGUGGCGGCCU | Downregulated | OSCP1,SP2,SOX2, HIST2H4A, HIST2H4B, BRCA1, CD4, SOD2 |
miR-6510-5p | −2,82 | CAGCAGGGGAGAGAGAGGAGUC | Downregulated | ABT1,BNC2,TPM3, COX6B1,AGO1, BCL2L13, MAP2K7 |
miR-6800-5p | −4,67 | GUAGGUGACAGUCAGGGGCGG | Downregulated | SERBP1,MYCBP, CDK2, DICER1 |
miR-7704 | −5,28 | CGGGGUCGGCGGCGACGUG | Downregulated | IFNAR1,KCNH1, SDF4, ERBB3, |
miR-8063 | −4,01 | UCAAAAUCAGGAGUCGGGGCUU | Downregulated | BCL2L11,AGO3, DNAJC21, E2F2, |
miR-8069 | −6,63 | GGAUGGUUGGGGGCGGUCGGCGU | Downregulated | BTG3,UBA6,RPS27,CCND1,CDK2AP2, DICER1, HHLA1 |
miRNAs | Fold change (FC) values | Sequence of miRNA | miRNAStatus | Target genes |
---|---|---|---|---|
let-7a-5p | 10,8 | UGAGGUAGUAGGUUGUAUAGUU | Upregulated | NF2,KRAS,HMGA2,HMGA1,CDK6, NRAS |
let-7b-5p | 3,79 | UGAGGUAGUAGGUUGUGUGGUU | Upregulated | HMGA1, IGF2BP1, CDC34, HMGA2, CDC25A, IGF2BP2 |
miR-181a-5p | 3,2 | AACAUUCAACGCUGUCGGUGAGU | Upregulated | CDKN1B,ATM,BCL2,KRAS, MAPK1 BRCA1,CDH13,KRAS,MMP14, NOTCH1, NOTCH2 |
miR-197-3p | 2,8 | UUCACCACCUUCUCCACCCAGC | Upregulated | CD82, PMAIP1, MTHFD1, RAD51, AGO1, CASP10, CHECK1 |
miR-21-5p | 6,75 | UAGCUUAUCAGACUGAUGUUGA | Upregulated | CDC25A,BCL2, PTEN, APAF1, E2F1, TP53, MSH2 |
miR-223-3p | 6,55 | UGUCAGUUUGUCAAAUACCCCA | Upregulated | IGF1R, PARP1 E2F1,CDK2, ATM, STAT5A, E2F1 |
miR-23a-3p | 5,98 | AUCACAUUGCCAGGGAUUUCC | Upregulated | MYH1,MYH2,MYH4,PTEN, APAF1, FOXO3, CDH1, MYC |
miR-27a-3p | 17,2 | UUCACAGUGGCUAAGUUCCGC | Upregulated | FOXO1, SP1, APC, EGFR, CCND1, CDH6, NF1, NRAS, TP53, WNT9B |
miR-3653-3p | 3,3 | CUAAGAAGUUGACUGAAG | Upregulated | CCND2, MYLIP, MTMR4, SMAD5, PTEN |
miR-425-5p | 6,08 | AAUGACACGAUCACUCCCGUUGA | Upregulated | CCND1, PTEN, FGFR3, DICER1, E2F3, MAP2K6, NRAS |
miR-572 | 3,34 | GUCCGCUCGGCGGUGGCCCA | Upregulated | CDKN1A, MED29, WNT7A, ATM |
miR-574-5p | 3,46 | UGAGUGUGUGUGUGUGAGUGUGU | Upregulated | FOXN3, PPP2R1B, BCL10, CCND1, CDH12, CDK15, CDKN1A, MAPK10 |
miR-6127 | 2,32 | UGAGGGAGUGGGUGGGAGG | Upregulated | TUBB2A,MYH14, DLX6, HIP, CHRDL1 |
miR-7641 | 3,14 | UUGAUCUCGGAAGCUAAGC | Upregulated | TRIP4,TAOK1,ARL5C,COX20, PPWD1, SLC30A4 |
let-7i-5p | −11,7 | UGAGGUAGUAGUUUGUGCUGUU | Downregulated | TLR4, BMP4, EIF2C1, NEUROG1, SOCS1, IL13, IGF1 |
miR-125a-5p | −4,11 | UCCCUGAGACCCUUUAACCUGUGA | Downregulated | ERBB3, CDKN1A, TP53, ERBB2, EGFR, STAT3, MYC, VEGFA |
miR-15b-5p | −3,08 | UAGCAGCACAUCAUGGUUUACA | Downregulated | BCL2,VEGFA,CCND1,CCNE1, CDK1, CDK4, CDK6, E2F3, MAPK1 |
miR-150-5p | −2,77 | UCUCCCAACCCUUGUACCAGUG | Downregulated | EGR2, ZEB1, MUC4,MYB, TP53, BIRC5 |
miR − 22-3p | −2,99 | AAGCUGCCAGUUGAAGAACUGU | Downregulated | CDKN1A, WNT1, ERBB3, MYCBP, HMGB1, BMP6, E2F2, PTEN |
miR-328-3p | −2,17 | CUGGCCCUCUCUGCCCUUCCGU | Downregulated | CD44, MMP16, AGO1, RAD51 |
miR-4430 | -2,35 | AGGCUGGAGUGAGCGGAG | Downregulated | ZNF485, ABL2, MAPK1, MSH5,PTEN |
miR-451a | −37,8 | AAACCGUUACCAUUACUGAGUU | Downregulated | CPNE3, RAB5A, IL6R, AKT1, MMP2 |
miR-4697 − 5p | -5,5 | AGGGGGCGCAGUCACUGACGUG | Downregulated | SIX5, BCL7A, MEN1,VGF |
miR-664b-5p | −2,89 | UGGGCUAAGGGAGAUGAUUGGGUA | Downregulated | CD55, MSN, RHOBTB3, PLAG1 |
miR-766-3p | −2,5 | ACUCCAGCCCCACAGCCUCAGC | Downregulated | COX1, MAPK1, NF2, RAD51, STK4, STK24, VEGFC |