HMGA2 plays an important role in Cr (VI)-induced autophagy

International Journal of Cancer. Journal International Du Cancer
Fan YangJun Cao

Abstract

Cr (VI) is mutagenic and carcinogenic, but the mechanism is unclear. In this study, the involvement of high mobility group A2 (HMGA2) in Cr (VI)-induced autophagy was investigated. Cr (VI) treatment induced formation of autophagosomes, increased expression of LC3II, Atg12-Atg5, Atg4, Atg10, HMGA1 and HMGA2 proteins, and decreased the expression of p62 in A549 cells. Silencing of HMGA2 gene by siRNA blocked Cr (VI)-induced formation of autophagosomes, expression of LC3II, Atg12-Atg5, Atg10 and reduction of p62. Overexpression of HMGA2 in HEK 293 and HeLa cells could induce the expression of LC3II, Atg12-Atg5 and Atg10, and decrease the expression of p62. Although the protein level of Atg12-Atg5 conjugation changed after Cr (VI) treatment, silencing of HMGA2 and overexpression of HMGA2, both the proteins and mRNA levels of Atg12 and Atg5 were not changed significantly. ChIP assay demonstrated that HMGA2 protein directly bound to the promoter sequence of Atg10 gene, which modulated the conjugation of Atg12-Atg5. Interestingly, 3-MA markedly prevented Cr (VI)-induced cell growth of A549 cells. Our further in vivo study confirmed that the expression of HMGA1, HMGA2, LC3II, Atg12-Atg5, Atg4, Atg5, Atg7, Atg10, Atg12, Beclin 1 were in...Continue Reading

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Citations

Jun 28, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Binya LiuQin Yan
Dec 21, 2018·Molecular Medicine Reports·Jiangtao SunHaiwen Wang
May 23, 2020·Biological Trace Element Research·Yue WangJianzhu Liu
Apr 25, 2020·Environmental Science and Pollution Research International·Yue WangJianzhu Liu
Oct 18, 2020·Translational Oncology·Xin WangJingjing Wu
Jul 31, 2021·Biological Trace Element Research·Kangping LiuJianzhu Liu

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