Table 5.

Biological pathways targeted by the 6 intervention-associated miRNAs in the LEAN trial^a

Pathway Name	LEAN p-value	LEAN Ratio genes/pathway	# genes	# in IPA pathway	Genes within Respective Pathway
Molecular mechanisms of cancer	6.8*10^−7	0.18	67	368	JAK1, BMPR2, WNT16, E2F3, MAPK11, CCND1, BCL2, TGFBR2, RB1, E2F5, AKT3, PRKCE, PIK3R2, E2F2, PMAIP1, RHOC, CDK6, RHOJ, BAX, BAK1, GNAI3, CCNE1, RHOV, MAX, MAPK14, CBL, RABIF, NF1, IRS1, CDKN1A, E2F1, PAK5, BMP7, BCL2L11, PSEN1, PRKCB
Estrogen mediated S-phase entry	1.4*10^−6	0.67	16	24	RB1, CCNE1, E2F1, CDKN1A, E2F5, E2F3, CCND1, ESR1, E2F2
Pancreatic adenocarcinoma signaling	1.5*10^−5	0.26	31	118	JAK1, STAT3, E2F3, CCND1, BCL2, TGFBR2, VEGFA, RB1, CCNE1, IRS1, E2F1, CDKN1A, E2F5, AKT3, PIK3R2, E2F2
Glioblastoma multiform signaling	2.0*10^−5	0.23	36	158	TSC1, RHOC, CDK6, WNT16, RHOJ, E2F3, CCND1, PDGFB, PTEN, PLCD1, RB1, RHOV, CCNE1, NF1, IRS1, E2F1, CDKN1A, E2F5, AKT3, PIK3R2, E2F2
Colorectal Cancer Metastasis Signaling	4.1*10^−5	0.19	45	242	MAP2K4, FZD10, JAK1, TGFBR1, MMP3, FZD3, SMAD3, MMP13, HRAS, GNG13, KRAS, IL6, CCND1, WNT8B, MYC, TGFBR2, VEGFA, APPL1, RHOG, RHOB, TLR7, SMAD4, TLR3, GNG5, PTGER4, TP53, IFNG, NRAS, CASP3, GRB2, RHOC, WNT9A, ADCY3, PRKAR2A, VEGFC, MMP10, BAX, STAT3, PIK3R3, BCL2L1, TLR4, GAB1, PTGS2, TNF, WNT1
Cell cycle: G 1/S Checkpoint regulation	5.5*10^−5	0.33	21	63	RB1, RBL2, CCNE1, MAX, HDAC8, E2F1, CDKN1A, E2F5, CDK6, E2F3, CCND1, E2F2
Chronic Myeloid Leukemia Signaling	1.3*10^−4	0.25	26	103	TGFBR2, RB1, RBL2, HDAC8, IRS1, CRKL, E2F1, CDKN1A, E2F5, CDK6, AKT3, PIK3R2, E2F3, CCND1, E2F2
Aryl Hydrocarbon Receptor Signaling	1.5*10^−4	0.22	30	135	CDKN2A, IL1A, NFIX, CDK4, IL6, CCND1, FAS, MYC, RB1, CTSD, CCNA2, NCOA7, FASLG, TP53, CCNE2, RBL2, CDK6, BAX, NCOA3, CYP1B1, CCND2, NFIA, E2F1, CDKN1A, NFIB, DHFR, CDKN1B, RXRA, TNF, ESR1
Glioma signaling	2.2*10^−4	0.24	26	109	RBL2, CDK6, E2F3, CCND1, PDGFB, PTEN, RB1, IRS1, E2F1, CDKN1A, E2F5, AKT3, PRKCE, PIK3R2, E2F2, PRKCB
P53 signaling	2.7*10^−4	0.24	26	111	PMAIP1, TP63, TNFRSF10B, PERP, BAX, CCND1, PTEN, BCL2, CCNG1, RB1, RHOV, CCNE1, NF1, IRS1, E2F1, SIRT1, AKT3, PIK3R2

Pathway analyses created using Ingenuity Pathway Analysis software (Qiagen, Inc.)

Abbreviations: LEAN: Lifestyle, Exercise and Nutrition

^ap value <0.0005 considered significant