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{"sheet":"Index","index":0,"n_rows":9,"n_cols":3,"rows_kept":9,"cut":false,"hidden":false,"merged":[],"flags":["formulas_cached_only"]}
["Index of Supplementary Information"]
[]
["No.","Worksheet Name","Description"]
[1,"Dysregulated miRNAs","List of miRNAs up-regulated and down-regulated in breast cancer that was used in this study"]
[2,"Target Pathways ( C )","Pathways collectively targeted by all dysregulated miRNAs"]
[3,"Target Pathways (U, C)","Pathways collectively targeted by up-regulated miRNAs"]
[4,"Target Pathways (D, C)","Pathways collectively targeted by down-regulated miRNAs"]
[5,"Target Pathways (U, I)","Pathways targeted by individual up-regulated miRNAs"]
[6,"Target Pathways (D, I)","Pathways targeted by individual down-regulated miRNAs"]

{"sheet":"Dysregulated miRNAs","index":1,"n_rows":32,"n_cols":8,"rows_kept":32,"cut":false,"hidden":false,"merged":[],"flags":["formulas_cached_only"]}
[]
[]
["List of miRNAs up-regulated in breast cancer"]
["miRNA ID","Source",null,"miRNA ID","Source",null,"miRNA ID","Source"]
["hsa-let-7e","Array",null,"hsa-miR-182","Array",null,"hsa-miR-29c","miR2Disease"]
["hsa-let-7f","miR2Disease",null,"hsa-miR-183","Array",null,"hsa-miR-373","miR2Disease"]
["hsa-let-7i","miR2Disease",null,"hsa-miR-184","Array",null,"hsa-miR-375","Array"]
["hsa-miR-106b","Array",null,"hsa-miR-185","Array",null,"hsa-miR-505","Array"]
["hsa-miR-136","Array",null,"hsa-miR-187","Array",null,"hsa-miR-510","miR2Disease"]
["hsa-miR-138","Array",null,"hsa-miR-18a","Array",null,"hsa-miR-9","Array"]
["hsa-miR-142-3p","Array",null,"hsa-miR-191","miR2Disease",null,"hsa-miR-93","Array"]
["hsa-miR-142-5p","Array",null,"hsa-miR-196a","Array",null,"hsa-miR-96","Array"]
["hsa-miR-148b","Array",null,"hsa-miR-202","miR2Disease",null,"hsa-miR-98","Array"]
["hsa-miR-149","miR2Disease",null,"hsa-miR-203","miR2Disease"]
["hsa-miR-155","miR2Disease",null,"hsa-miR-21","miR2Disease"]
["hsa-miR-15a","Array",null,"hsa-miR-210","Array"]
["hsa-miR-15b","Array",null,"hsa-miR-25","Array"]
["hsa-miR-181b","miR2Disease",null,"hsa-miR-27a","miR2Disease"]
["hsa-miR-181d","miR2Disease",null,"hsa-miR-29b","miR2Disease"]
[]
["List of miRNAs down-regulated in breast cancer"]
["miRNA ID","Source",null,"miRNA ID","Source",null,"miRNA ID","Source"]
["hsa-let-7a","miR2Disease",null,"hsa-miR-143","miR2Disease",null,"hsa-miR-335","miR2Disease"]
["hsa-let-7d","miR2Disease",null,"hsa-miR-145","miR2Disease",null,"hsa-miR-429","miR2Disease"]
["hsa-miR-1","Array",null,"hsa-miR-152","miR2Disease",null,"hsa-miR-451","miR2Disease"]
["hsa-miR-100","Array",null,"hsa-miR-200a","Array",null,"hsa-miR-497","Array"]
["hsa-miR-10a","Array",null,"hsa-miR-200b","miR2Disease",null,"hsa-miR-663","miR2Disease"]
["hsa-miR-125b","miR2Disease",null,"hsa-miR-200c","Array",null,"hsa-miR-99a","Array"]
["hsa-miR-126","miR2Disease",null,"hsa-miR-205","miR2Disease"]
["hsa-miR-130a","Array",null,"hsa-miR-20a","miR2Disease"]
["hsa-miR-135b","Array",null,"hsa-miR-30d","Array"]
["hsa-miR-141","Array",null,"hsa-miR-31","miR2Disease"]

{"sheet":"Target Pathways (C)","index":2,"n_rows":16,"n_cols":3,"rows_kept":16,"cut":false,"hidden":false,"merged":[],"flags":["formulas_cached_only"]}
["Pathways collectively targeted by dysregulated miRNAs"]
[]
["KEGG Pathway","p-value","Target Genes"]
["Pancreatic cancer",1.8e-05,"RAC1, TP53, ARHGEF6, TGFBR2, RAF1, CASP9, VEGFC, PIK3R1, CHUK, SMAD3, CDC42, CDK4, RALA, ARAF, CDKN2A, PIK3R2, MAPK10, RALBP1, RELA, STAT1, RB1, MAPK9, VEGFB, E2F2"]
["Dentatorubropallidoluysian atrophy (DRPLA)",0.000147,"ITCH, MAGI2, WWP2, CASP8, BAIAP2, WWP1, CASP3, RERE"]
["Chronic myeloid leukemia",0.000146,"TP53, TGFBR2, RAF1, SHC1, PIK3R1, CHUK, CTBP1, SMAD3, BCR, CDKN1B, CDK4, ARAF, SOS2, CDKN2A, ABL1, PIK3R2, SHC3, CRKL, RELA, RUNX1, RB1, E2F2"]
["Small cell lung cancer",0.001668,"COL4A6, LAMB3, TP53, CASP9, ITGB1, ITGA3, RXRA, PIK3R1, CHUK, CCNE1, ITGA6, CDKN1B, CDK4, PTK2, LAMA1, TRAF3, PIK3R2, CCNE2, RELA, RB1, FN1, E2F2"]
["Focal adhesion",0.001703,"COL4A6, ROCK1, LAMB3, ILK, RAC1, TLN1, FLT1, RAF1, FYN, ITGB1, VEGFC, COL5A2, SHC1, ITGA3, PIK3R1, PDPK1, ITGB4, CAV2, ITGB3, CDC42, MYLK, ITGA6, FLNB, PTK2, ITGB8, SOS2, PARVB, LAMA1, CAV1, JUN, PIK3R2, SHC3, MAPK10, CRKL, PPP1CB, FLNA, PIP5K1C, MAPK9, VEGFB, FN1"]
["Cell cycle",0.002324,"CDC27, TP53, YWHAH, CDC23, CDC25B, MAD1L1, SMAD3, CCNE1, CDKN1B, CDK4, RBL2, CDKN2A, ABL1, CCNE2, BUB1, SMC1A, MCM4, RB1, WEE1, CUL1, YWHAZ, CDKN1C, E2F2, CDC25A, FZR1"]
["p53 signaling pathway",0.004217,"EI24, SERPINE1, TP53, SERPINB5, CASP9, RCHY1, CCNE1, FAS, CDK4, IGFBP3, CCNG1, RRM2, CDKN2A, CASP8, CCNE2, GTSE1, CASP3"]
["Regulation of actin cytoskeleton",0.005648,"RRAS2, ROCK1, WASL, RAC1, RDX, ARHGEF6, VIL2, RAF1, GSN, FGFR1, ITGB1, FGFR2, PIP5K1A, ITGA3, PIK3R1, ITGB4, ITGB3, CDC42, MYLK, ITGA6, PIP5K1B, PTK2, ITGB8, FGF2, ARAF, SOS2, GNA12, F2R, PIK3R2, CRKL, PPP1CB, GNG12, FGF1, PIP5K1C, PIP5K3, BAIAP2, ARPC3, FGF5, FN1"]
["MAPK signaling pathway",0.005543,"RRAS2, HSPB1, PTPRR, RAC1, TP53, RAPGEF2, TGFBR2, MAP3K8, RAF1, FGFR1, DUSP14, DUSP3, HSPA1B, FGFR2, MAPKAPK2, PPP5C, CDC25B, NTRK2, CHUK, PRKX, CDC42, MAPKAPK3, FLNB, FAS, FOS, RPS6KA4, MAP4K4, FGF2, SOS2, GNA12, JUN, MAPK10, CRKL, GNG12, FLNA, NTF3, FGF1, DUSP10, PRKY, FGF5, MAPK9, RPS6KA2, MAPK8IP1, CASP3, MAP2K6"]
["Prostate cancer",0.014472,"TP53, RAF1, CASP9, FGFR1, FOXO1A, FGFR2, PIK3R1, CHUK, PDPK1, CCNE1, CREB1, CDKN1B, ARAF, SOS2, PIK3R2, CCNE2, RELA, RB1, E2F2"]
["Pathogenic Escherichia coli infection - EPEC",0.022131,"ROCK1, WASL, VIL2, FYN, ITGB1, TUBA1A, TUBB4, CDC42, NCK2, CDH1, ABL1, YWHAZ"]
["Endometrial cancer",0.049795,"ILK, TP53, RAF1, CASP9, CTNNA1, PIK3R1, PDPK1, CDH1, ARAF, SOS2, PIK3R2"]
["Inositol phosphate metabolism",0.04812,"PLCE1, INPPL1, PIP5K1A, SYNJ2, INPP1, PIP5K1B, ITPKB, PIP5K1C, PIP5K3, INPP5A"]

{"sheet":"Target Pathways (U, C)","index":3,"n_rows":11,"n_cols":3,"rows_kept":11,"cut":false,"hidden":false,"merged":[],"flags":["formulas_cached_only"]}
["Pathways collectively targeted by up-regulated miRNAs"]
[]
["KEGG Pathway","p-value","Target Genes"]
["TGF-beta signaling pathway",0.001483,"ROCK1, SKP1A, RBL2, ID3, TGFBR2, THBS1, LTBP1, PPP2CB, BMPR1A, ID2, SMAD5, SMURF2, PPP2CA"]
["Neurodegenerative diseases",0.006196,"PINK1, PSEN1, NGFR, PRNP, APP, NEFH, CASP3"]
["Focal adhesion",0.003865,"COL4A6, ROCK1, ITGB8, PAK1, SOS2, FYN, CAV1, THBS1, ITGB1, VEGFC, MAPK10, PPP1CB, SHC1, ITGA3, PIK3R1, CAV2, ITGB3, MYLK, FN1, ITGA6, FLNB"]
["Regulation of actin cytoskeleton",0.004172,"RRAS2, ROCK1, ITGB8, PAK1, RDX, VIL2, SOS2, F2R, ITGB1, FGFR2, PPP1CB, ITGA3, GNG12, FGF1, PIK3R1, PIP5K3, ARPC3, FGF5, ITGB3, MYLK, FN1, ITGA6"]
["Pathogenic Escherichia coli infection - EPEC",0.028402,"CDH1, ROCK1, VIL2, FYN, ITGB1, TUBA1A, YWHAZ"]
["Pathogenic Escherichia coli infection - EHEC",0.028402,"CDH1, ROCK1, VIL2, FYN, ITGB1, TUBA1A, YWHAZ"]
["p53 signaling pathway",0.037597,"EI24, CCNG1, SERPINB5, THBS1, CCNE2, RCHY1, CASP3, FAS"]
["Biosynthesis of steroids",0.046094,"HMGCR, DHCR24, FDFT1, SC5DL"]

{"sheet":"Target Pathways (D, C)","index":4,"n_rows":15,"n_cols":3,"rows_kept":15,"cut":false,"hidden":false,"merged":[],"flags":["formulas_cached_only"]}
["Pathways collectively targeted by down-regulated miRNAs"]
[]
["KEGG Pathway","p-value","Target Genes"]
["Chronic myeloid leukemia",4.6e-05,"RELA, CTBP1, TP53, ARAF, SMAD3, RAF1, CDKN2A, BCR, PIK3R2, ABL1, CRKL"]
["Pancreatic cancer",0.000163,"RELA, TP53, ARAF, SMAD3, RAF1, MAPK9, CDKN2A, CASP9, CDC42, PIK3R2"]
["Non-small cell lung cancer",0.000426,"RXRA, PDPK1, TP53, ARAF, RAF1, CDKN2A, CASP9, PIK3R2"]
["Prostate cancer",0.003602,"PDPK1, RELA, TP53, ARAF, RAF1, CASP9, FGFR1, CCNE1, PIK3R2"]
["Endometrial cancer",0.007921,"PDPK1, TP53, ARAF, RAF1, CASP9, PIK3R2"]
["Renal cell carcinoma",0.007932,"ARNT, EPAS1, ARAF, RAF1, CDC42, PIK3R2, CRKL"]
["Colorectal cancer",0.007969,"DVL1, TP53, ARAF, SMAD3, RAF1, MAPK9, CASP9, PIK3R2"]
["Melanoma",0.009986,"TP53, FGF2, ARAF, RAF1, CDKN2A, FGFR1, PIK3R2"]
["Cell cycle",0.012916,"SMC1A, MAD1L1, TP53, SMAD3, CDKN2A, WEE1, CCNE1, ABL1, CDC25A"]
["Phosphatidylinositol signaling system",0.032769,"PIP5K1C, INPPL1, SYNJ2, ITPKB, PIK3R2, PIK3C2B"]
["Adherens junction",0.043559,"WASL, BAIAP2, SMAD3, ACP1, FGFR1, CDC42"]
["MAPK signaling pathway",0.043847,"PPP5C, FLNA, NTRK2, PTPRR, TP53, FGF2, RAF1, MAPK9, GNA12, FGFR1, CDC42, HSPA1B, DUSP3, CRKL"]

{"sheet":"Target Pathways (U, I)","index":5,"n_rows":27,"n_cols":5,"rows_kept":27,"cut":false,"hidden":false,"merged":[[18,0,18,4],[21,0,21,4],[24,0,24,4],[2,0,2,4],[6,0,6,4],[10,0,10,4],[14,0,14,4]],"flags":["formulas_cached_only"]}
["Pathways individually targeted by up-regulated miRNAs"]
[]
["hsa-miR-142-5p"]
["Pathway","Expected","Actual","p-value","Target Genes"]
["Ribosome",1,4,0.044569,"RPS25, RPL37A, RPL12, RPL6"]
["TGF-beta signaling pathway",1,6,0.006547,"ROCK1, BMPR1A, RBL2, TGFBR2, SMAD5, LTBP1"]
["hsa-miR-155"]
["Pathway","Expected","Actual","p-value","Target Genes"]
["Ubiquitin mediated proteolysis",1,4,0.005898,"RCHY1, UBE2D3, PPIL2, SMURF2"]
["Glutamate metabolism",0,3,0.000868,"GLS, GLUL, ABAT"]
["hsa-miR-183"]
["Pathway","Expected","Actual","p-value","Target Genes"]
["Regulation of actin cytoskeleton",1,5,0.019481,"GNG12, VIL2, FN1, MYLK, ITGB1"]
["Long-term depression",0,3,0.017221,"PPP2CB, GUCY1A3, PPP2CA"]
["hsa-miR-203"]
["Pathway","Expected","Actual","p-value","Target Genes"]
["Focal adhesion",2,7,0.033482,"PPP1CB, SHC1, CAV2, FYN, CAV1, FLNB, MAPK10"]
["Insulin signaling pathway",2,6,0.017151,"PPP1CB, SHC1, PRKCI, PRKY, GYS1, MAPK10"]
["hsa-miR-21"]
["Pathway","Expected","Actual","p-value","Target Genes"]
["Acute myeloid leukemia",1,3,0.035309,"PIK3R1, CHUK, SOS2"]
["hsa-miR-25"]
["Pathway","Expected","Actual","p-value","Target Genes"]
["Regulation of actin cytoskeleton",2,5,0.041072,"PIK3R1, FGF1, PIP5K3, ITGB3, ITGA6"]
["hsa-miR-27a"]
["Pathway","Expected","Actual","p-value","Target Genes"]
["Glutamate metabolism",0,3,0.007627,"ALDH4A1, GLS, ABAT"]

{"sheet":"Target Pathways (D, I)","index":6,"n_rows":14,"n_cols":5,"rows_kept":14,"cut":false,"hidden":false,"merged":[[2,0,2,4],[8,0,8,4]],"flags":["formulas_cached_only"]}
["Pathways individually targeted by down-regulated miRNAs"]
[]
["hsa-miR-497"]
["Pathway","Expected","Actual","p-value","Target Genes"]
["MAPK signaling pathway",4,9,0.029166,"RAF1, MAPK9, GNA12, NTRK2, FGFR1, CDC42, PTPRR, HSPA1B, CRKL"]
["Prostate cancer",2,5,0.019639,"RAF1, PDPK1, FGFR1, CCNE1, PIK3R2"]
["Renal cell carcinoma",1,5,0.016442,"ARNT, RAF1, CDC42, PIK3R2, CRKL"]
["Regulation of actin cytoskeleton",3,8,0.03165,"RAF1, GNA12, FGFR1, CDC42, WASL, PIK3R2, BAIAP2, CRKL"]
["hsa-miR-663"]
["Pathway","Expected","Actual","p-value","Target Genes"]
["Non-small cell lung cancer",0,4,0.041644,"CDKN2A, RXRA, PDPK1, ARAF"]
["Phosphatidylinositol signaling system",1,4,0.005819,"PIP5K1C, INPPL1, SYNJ2, ITPKB"]
["Chronic myeloid leukemia",1,4,0.008519,"CDKN2A, CTBP1, ARAF, SMAD3"]
["Inositol phosphate metabolism",0,4,0.000653,"PIP5K1C, INPPL1, SYNJ2, ITPKB"]