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. 2021 Feb 13;12(2):269. doi: 10.3390/genes12020269

Figure 4.

Figure 4

HMGA2 promotes cancer cell proliferation, inhibits apoptosis, and differentially affects DNA damage repair. (A) HMGA2 activates cyclin D1, cyclin E, and cyclin A and promotes pRB phosphorylation. This releases E2 promoter-binding factor 1 (E2F1), enabling it to induce transcription of target genes that promote S phase entry. HMGA2 directly activates E2F1 by replacing histone deacetylase 1 (HDAC1) from pRB. HMGA2 also triggers proliferation by inducing cyclin B2. (B) HMGA2 negatively regulates proapoptotic proteins, including caspase-2, -3, and -9, and induces antiapoptotic Bcl2. HMGA2 also promotes AKT signaling, which suppresses BAX/BAK and caspase-9 activation. (C) HMGA2 triggers γ-H2AX and human AP endonuclease 1 (APE1) and inhibits Ku-80 and ataxia telangiectasia mutated protein (ATM), thereby promoting DNA damage. In contrast, by activating ATM, ataxia telangiectasia, and Rad3-related kinase (ATR), and checkpoint kinase 1 (CHK1), HMGA2 also promotes DNA repair. miR-182 is an oncogenic miRNA that promotes DNA repair by inducing HMGA2.