MicroRNA-Mediated Regulation of HMGB1 in Human Hepatocellular Carcinoma

Table 1

List of microRNAs involved in HMGB1 signaling pathways.

miRNA	Binding site	Biological effects on HMGB1	Biological effects on phenotype	Possible involved signaling pathway	Clinical significance	Cell lines	Animal model	Ref
miR-200a	lncRNA-TP73-AS1 3′UTR of HMGB1 mRNA (position 2724–2730)	miR-200a negatively regulates HMGB1 expression.; TP73-AS1 competes with HMGB1 for miR-200a binding.	Inhibition of cell proliferation	HMGB1/RAGE and NF-кB targets cytokines	High lncRNA-TP73- AS1 expression in HCC is correlated with poorer prognosis.	HCCLM3, MHCC97L, SMMC772, Hep3B, HepG2	-	[37]
miR-320a	3′UTR of HMGB1 mRNA	miR-320a suppresses the expression of HMGB1.	Suppressing the invasion and metastasis of cells	HMGB1-RAGE-MMP2/MMP9 signaling	The decrease of miR-320a is associated with the invasion and metastasis.	HepG2, SK-hep-1	-	[38]
miR-505	3′UTR of HMGB1 mRNA (positions 417–424)	miR-505 negatively regulates HMGB1 expression in cells.	Inhibition of cell proliferation, invasion, and EMT	TGF-β-induced EMT	-	QGY7703, SMMC7721, MHCC97	-	[39]
miR-129-2	3′UTR of HMGB1 mRNA (positions 387–394)	HMGB1 is a downstream mediator of the biological function of miR-129-2.	Suppressing HCC migration and invasion	HMGB1-pAKT-MMP2; /MMP9 signaling	miR-129-2 is inversely correlated with venous infiltration, high Edmondson-Steiner grading, and advanced TNM stage.; An independent prognostic factor for OS/DFS.	HepB3, Huh7	BALB/c nude mice	[40]
miR-325	3′UTR of HMGB1 mRNA	miR-325 negatively regulates HMGB1 expression.	Inhibition of cell invasion and proliferation	-	miR-325 is highly associated with HCC tumor size, TNM stage, and metastasis of patients.; An independent prognostic factor for OS.	SMMC-7721, Hep3B, HepG2, Huh7, Bel7404	-	[41]
miR-21	3′-UTRs of RECK and TIMP3 mRNA	HMGB1 signaling increases miR-21 expression to mediate the enhanced activity of MMPs through RECK/TIMP3.	Promoting cell invasion, migration, and proliferation	HMGB1-IL-6/Stat3 signalingRECK/TIMP3-MMP	-	Primary HCC cells, Huh7, HepG2, HepB3	Athymic nude mice	[30]

3′UTR: 3′ untranslated region; RAGE: receptor for advanced glycation end-products; MMP: matrix metalloproteinases; EMT: epithelial-mesenchymal transition; TNM: tumor-node-metastasis; OS: overall survival; DFS: disease-free survival; RECK: reversion-inducing cysteine-rich protein with Kazal motifs; TIMP3: metalloproteinase inhibitor 3. Ref: references.