Hepatitis B virus and microRNAs: Complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases

Table 3 Hepatitis B virus-mediated regulation of cellular microRNAs

miRNA	Regulation	Sample type	Proposed target	Proposed targeted pathway	Method of detection	Ref.
HBV-mediated regulation
miR-122	Down	HepG2.2.15	HO-1	Inflammation and apoptosis	qRT-PCR	[151]
	Down	HBV-transfected HepG2/Huh7/SK-Hep-01, HBV-transgenic mice, HBV-infected liver tissue	PBF	Cell proliferation	qRT-PCR	[69]
	Down	HepG2.2.15	Cyclin G1	Cell cycle regulation; p53-mediated repression of HBV transcription	In-situ hybridization, qRT-PCR	[98]
	Down	HepG2.2.15	NDGR3	Cell proliferation	qRT-PCR	[95]
	Up	HBV-infected primary treeshrew hepatocytes, HBV patient serum	-	-	Next-generation sequencing, qRT-PCR	[66]
	Up	HBV patient serum	-	-	microarray	[77,159]
let-7a/g	Down	HBV-transfected HepG2	-	-	microarray	[84]
let-7a	Down	HBV-transfected HepG2	-	-	qRT-PCR	[106]
let-7 family	Up	HepG2.2.15	-	-	microarray	[84]
let-7a	Up	HepG2.2.15	-	-	microarray	[81]
miR-15/16 family	Down	HBV-transfected HepG2	-	-	microarray	[84]
	Down	HBV-transfected HepG2, HepG2.2.15, HBV-transgenic mice, HBV-associated HCC	Bcl-2	Apoptosis	qRT-PCR	[70]
	Down	HepG2.2.15	-	-	microarray	[83]
miR-22	Down	HepG2.2.15	CDKN1A	Cell proliferation	qRT-PCR	[167]
miR-29c	Down	HepG2.2.15	TNFAIP3	Cell proliferation	qRT-PCR	[166]
miR-125a-5p	Up	HBV-infected liver tissue	-	-	qRT-PCR	[121]
	Up	HepG2.2.15	-	-	microarray	[82,83]
	Up	Transfected Cell Line	-	-	qRT-PCR	[106]
miR-125b	Down	HepG2.2.15, HBV-transfected HepG2	SCCND1	-	microarray, qRT-PCR	[123]
miR-181a	Up	HepG2.2.15, AdHBV-infected HepG2	E2F5	Cell proliferation	qRT-PCR	[138]
mIR-199b	Down	HBsAg+ liver tissue	-	-	microarray	[82]
miR-372/373	Up	HepG2.2.15	NFIB	HBV replication	microarray	[82]
miR-501	Up	HepG2.2.15	HBXIP	HBV replication	microarray, qRT-PCR	[81]
miR-602	Up	HepG2.2.15	RASSF1A	Apoptosis, tumor suppressor	microarray, qRT-PCR	[99]
HBx-mediated regulation
miR-122	Down	HBx-expressing HepG2	PPARγ	miR-122 transcription	qRT-PCR	[97]
let-7 family	Down	HBx over-expressing HepG2, HCC	Stat3	Cell proliferation	microarray, qRT-PCR	[107]
miR-15/16 family	Down	HBx-expressing HepG2/Huh7/SK-HEP-1 cells	CyclinD1	Cell cycle	microarray, qRT-PCR	[129]
miR-21	Up	HBx-expressing HepG2/Huh7	PDCD4, PTEN	Akt, cell proliferation	qRT-PCR	[145]
miR-21	Up	HBx-expressing MIHA	-	Cell migration	qRT-PCR	[187]
miR-29a	Up	HepG2.2.15, HBx-expressing HepG2, HBx-transgenic mice	PTEN	Akt, cell migration	qRT-PCR	[67]
miR-101	Down	HepG2.2.15, HBx-expressing HepG2	DNMT3A	DNA methylation	qRT-PCR	[147]
miR-143	Up	HBx-expressing HepG2, HBx-transgenic mice	FNDC3B	Cell proliferation	qRT-PCR	[168]
miR-148a	Down	HBx-expressing LO2/HepG2 cells	HPIP	mTOR	qRT-PCR	[144]
miR-152	Down	HepG2.2.15, HBx-expressing HepG2, HBx-transgenic mice	DNMT`1	DNA methylation	microarray, qRT-PCR	[188]
miR-199a	Up	HBx-expressing HepG2, HepG2.2.15, HBV infected HCC	-	-	microarray, qRT-PCR	[107]
miR-205	Down	HBx-expressing HepG2, HBV-associated HCC		DNA methylation, cell proliferation	qRT-PCR	[72]
miR-224	Up	HBx-transgenic mice	Smad4	Cell proliferation	in-situ hybridization, qRT-PCR	[68]
HBV-associated HCC
miR-122	Down	HBV-associated HCC	PBF	Cell proliferation	qRT-PCR	[69]
	Down	HBV-associated HCC	NDGR3	Cell proliferation	qRT-PCR	[95]
let-7 family	Down	HCC	Stat3	Cell proliferation	microarray, qRT-PCR	[107]
miR-199a/b-3p	Down	HCC liver samples (HBV and non-HBV)	PAK4	ERK, cell proliferation	NGS, qRT-PCR	[30]
miR-199b	Down	HBV-associated HCC	-	-	qRT-PCR	[74]
miR-22	Down	HBV-associated HCC	CDKN1A	Cell proliferation	qRT-PCR	[167]
miR-29c	Down	HBV-associated HCC	TNFAIP3	Cell proliferation	qRT-PCR	[166]
miR-101	Down	HBV-associated HCC	DNMT3A	DNA methylation	qRT-PCR	[147]
miR-143	Up	HBV-associated HCC	FNDC3B	Cell proliferation	qRT-PCR	[168]
miR-145	Down	HBV-associated HCC	-	-	qRT-PCR	[74]
miR-224	Up	HBV-associated HCC	-	-	qRT-PCR	[74]
miR-224	Up	HBV-associated HCC	Smad4	cell proliferation	in-situ hybridization, qRT-PCR	[68]
miR-501	Up	HBV-associated HCC	HBXIP	HBV replication	microarray, qRT-PCR	[81]
miR-602	Up	HCC liver samples (HBV and non-HBV)	RASSF1A	Apoptosis, tumor suppressor	microarray, qRT-PCR	[99]

HBV: Hepatitis B virus; HBx: Hepatitis B virus-X protein; HCC: Hepatocellular carcinoma; miRNA: microRNA; qRT-PCR: Quantitative reverse transcription polymerase chain reaction.