MicroRNAs in Hepatocellular Carcinoma: Regulation, Function, and Clinical Implications

Table 1

MiRNAs deregulated in hepatocellular carcinoma (HCC).

miRNA	Expression in HCC	Regulator	Target	Involvement in cellular processes	References
Let-7a	Down	c-myc	Caspase-3	apoptosis; proliferation	[42, 91]
Let-7b	Down		HMGA2	apoptosis; proliferation	[92]
Let-7c	Down	EZH2; PPARalpha	Bcl-xL; c-myc	apoptosis; proliferation; cell growth	[43, 93, 94]
Let-7d	Down	c-myc		apoptosis; proliferation	[42]
Let-7f-1	Down	c-myc		apoptosis; proliferation	[42]
Let-7g	Down		Bcl-xL; COL1A2; c-Myc; p16(INK4A)	apoptosis; metastasis	[73, 95, 96]
miR-1	Down		ET-1;	proliferation	[97]
miR-101	Down	EZH2	Mcl-1; EZH2; EED; DNMT3A; SOX9	Colon formation; apoptosis; DNA methylation	[43, 70, 98, 99]
miR-122	Down	PPFP	Bcl-w; ADAM17; Wnt1	apoptosis; metastasis; Angiogenesis;	[71, 88, 100, 101]
miR-124	Down		PIK3CA	proliferation	[102]
miR-125a	Down		MMP11; VEGF-A; SIRT7	proliferation; metastasis; metabolism	[103, 104]
miR-125b	Down	EZH2; p53	LIN28B2; PIGF; Bcl-2; Mcl-1; Bcl-w; SUV39H1; SIRT7	proliferation; metastasis; angiogenesis; apoptosis; histone modification	[43, 66, 90, 104–106]
miR-139	Down	EZH2	ROCK2; c-Fos	metastasis	[43, 107, 108]
miR-138	Down		CCND3	Cell cycle	[109]
miR-145	Down		IRS1; IRS2; Oct4	Cell growth; tumorigenesis	[110, 111]
miR-195	Down		cyclin D1; CDK6; E2F3; LATS2	tumorigenesis; cell cycle; apoptosis	[57, 112]
miR-199a-3p	Down		mTOR; PAK4; caveolin-2	drug resistance; Cell growth;	[80, 113, 114]
miR-199a-5p	Down		DDR1; ATG7	invasion; autophagy	[115, 116]
miR-200a	Down	HDAC4	HDAC4	proliferation; metastasis;	[117]
miR-203	Down		Surviving	proliferation	[118]
miR-214	Down		β-catenin; HDGF	Cell growth; metastasis; angiogenesis	[87, 119, 120]
miR-219-5p	Down		GPC3	proliferation	[121]
miR-223	Down		STMN1	proliferation	[61]
miR-26a/b	Down	c-myc	CDK6; cyclin E1	Cell cycle	[122]
miR-29a	Down		SPARC	proliferation	[123]
miR-34a	Down	TGF-β	c-Met; CCL22	metastasis	[85, 124]
miR-375	Down		ATG7	Autophagy	[125]
miR-376a	Down		PIK3R1	apoptosis; proliferation	[126]
miR-449	Down		c-Met	proliferation; apoptosis	[84]
miR-450a	Down		DNMT3a	proliferation	[127]
miR-520b	Down		MEKK2; cyclin D1	Cell growth; proliferation	[63]
miR-7	Down		PIK3CD; mTOR; p70S6K	Tumorigenesis; metastasis	[79]
miR-10a	Up		EphA4; CADM1	EMT; metastasis	[128, 129]
miR-130a	Up		RUNX3	drug resistance	[130]
miR-135a	Up	FOXM1	MTSS1	metastasis	[131]
miR-143	Up	NF-κB	FNDC3B	metastasis	[132]
miR-155	Up	NF-κB	APC	proliferation; Tumorigenesis	[133]
miR-18a	Up		ERalpha	proliferation	[38]
miR-181b	Up	Smad4	TIMP3	Cell growth; tumorigenesis; metastasis	[134]
miR-182	Up		MTSS1	metastasis	[135]
miR-21	Up		PTEN; RHOB; PDCD4	metastasis; drug resistance	[75, 136–138]
miR-210	Up		VMP1; AIFM3	metastasis; apoptosis; proliferation	[139, 140]
miR-216a	Up	Androgen receptor	TSLC1	tumorigenesis	[141]
miR-221	Up	SND1	Bmf; CDKN1B/p27; CDKN1C/p57; DDIT4; Arnt	apoptosis; proliferation; Angiogenesis	[64, 86, 142–144]
miR-224	Up	HDAC1; HDAC3; EP300; NFκB	RKIP; CDC42; CDH1; PAK2; BCL-2; MAPK1; API-5	Metastasis; proliferation; apoptosis	[68, 145–148]
miR-23a	Up	Stat3	PGC-1α; G6PC	Gluconeogenesis	[149]
miR-373	Up		PPP6C	Cell cycle	[150]
miR-301a	Up		Gax	metastasis	[151]
miR-490-3p	Up		ERGIC3	EMT	[152]
miR-519d	Up	p53	CDKN1A/p21; PTEN; AKT3; TIMP2	proliferation; invasion; apoptosis	[77]
MiR-550a	Up		CPEB4	Metastasis	[153]
miR-590-5p	Up		TGF-beta RII	Metastasis; proliferation	[154]
miR-615-5p	Up		IGF-II	Cell growth; migration	[155]
miRNA-657	Up		TLE1	proliferation	[156]