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] |
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| 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] |
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| 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] |
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| 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] |
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| 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.