Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma

Table 1 miRNAs involved in hepatitis B virus infection

miRNA	Validated target	Effect on HBV	Ref.
miRNA targeting HBV transcripts
miR-15a/miR-16-1	HBx	↓	[28,33]
miR-20a/miR-92a-1	Polymerase/HBx	↓	[29]
miR-122	Polymerase/HBc	↓	[27]
miR-125a	HBsAg	↓	[23-26,32]
miR-199a-3p	HBsAg	↓	[22]
miR-205	HBx	↓	[31]
miR-210	HBsAg pre-S1 region	↓	[22]
miR-1231	HBc	↓	[30]
miRNAs targeting HBV regulators
miR-1	HDAC4	↑	[51-53]
miR-15b	HNF1	↑	[50]
miR-34a	CCL22	↓	[60]
miR-122	Cyclin G1	↑	[43-45]
	HO-1		[45,46]
miR-130a	PGC1 PPAR	↓	[41]
miR-141	PPAR	↓	[24,40]
miR-146a	STAT1	↑	[58]
miR-152	DNMT-1	↑	[54-57]
miR-155	C/EBP	↓	[35-38]
	SOCS1	↓	[39]
miR-370	NFIA	↑	[49]
miR-372/373	NFIB	↑	[48]
miR-501	HBXIP	↑	[42]
miR-548a	IFNλ-1	↑	[59]

MiRNAs are listed according to their increasing number name. ↓: Suppress HBV infection; ↑: Promote HBV infection; HBV: Hepatitis B virus.

Table 2 MicroRNAs playing oncogenic or oncosuppressive roles in hepatocellular carcinoma

MicroRNA	Expression in HCC	Cellular effects	Direct targets in HCC	Ref.
let-7 family	Downregulated	Proliferation (-)	Bcl-xL, c-Myc, collagen type 1α2, RAS, STAT3	[89,132-136]
		migration (-)
		apoptosis (+)
miR-21	Upregulated	Proliferation (+) migration (+) apoptosis (-)	IL-12, HBP1, PDCD4, PTEN, RECK, TIMP-3	[72,137-141]
miR-29	Downregulated	Proliferation (-) apoptosis (+)	Bcl-2, lncRNA MEG3, Mcl-1, SIRT1	[80,142,143]
miR-99a	Downregulated	Proliferation (-)	AGO2, IGF1R, mTOR	[144-147]
miR-122	Downregulated	Proliferation (-)	ADAM17, c-Myc, CUTL1, CCNG1, WNT1	[145,148-153]
		migration (-)
miR-125a	Downregulated	Proliferation (-) migration (-) angiogenesis (-)	c-RAF, LIN28B, MMP11, SIRT7, VEGFA, Zbtb7a	[72,123,145,154-159]
miR-125b	Downregulated	Proliferation (-)	Bcl-2, LIN28B, SIRT7	[72,145,157,160-162]
		apoptosis (+)
miR-155	Upregulated	Proliferation (+) migration (+)	ARID2, C/EBPbeta, PTEN, SOCS1, SOX6	[38,163-165]
miR-199a-3p	Downregulated	Proliferation (-) apoptosis (+)	CD44, CD51, c-MET, mTOR, PAK4, YAP1, ZHX1	[71-78,154]
miR-221	Upregulated	Proliferation (+) apoptosis (-)	BMF, Caspase-3, CDKN1B, CDKN1C, DDIT4	[166-169]

ADAM17: Disintegrin and metalloprotease 17; AGO2: Argonaute-2 protein; Bcl-2: B-cell lymphoma 2 protein; ARID2: AT-rich interactive domain 2; BMF: Bcl-2-modifying factor; C/EBPbeta: CCAT/enhancer binding protein beta; CCNG1: Cyclin-G1; CDKN: Cyclin-dependent kinase inhibitor; DDIT4: DNA-damage inducible transcript 4; HBP1: HMG-box transcription factor 1; IGF1R: Insulin-like growth factor 1 receptor; IL-12: Interleukin-12; Mcl-1: Induced myeloid leukemia cell differentiation protein 1; PAK4: Serine/threonine-protein kinase 4; PDCD4: Programmed cell death protein 4; PTEN: Phosphatase and tensin homolog; RECK: Reversion-inducing-cysteine-rich protein with kazal motifs; SIRT: Sirtuin; SOCS1: Suppressor of cytokine signaling 1; STAT3: Signal transducer and activator of transcription 3; TIMP3: Metalloproteinase inhibitor 3; VEGFA: Vascular endothelial growth factor A; YAP1: Yes-associated protein 1; Zbtb7a: Zinc finger and BTB domain-containing protein 7A; ZHX1: Zinc-fingers and homeoboxes-1.