XPA serves as an autophagy and apoptosis inducer by suppressing hepatocellular carcinoma in a PI3K/Akt/mTOR dependent manner

Journal of Gastrointestinal Oncology

article

Yi Deng¹  Qing-Song Chen¹  Wei-Feng Huang¹  Jiang-Wen Dai¹  Zhong-Jun Wu¹ 

[1] Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University;Department of Oncology, Yongchuan Hospital of Chongqing Medical University;Department of Traumatology, Chongqing University Central Hospital;Department of Oncology, Chengdu Fifth People’s Hospital

关键词: XPA;    autophagy;    apoptosis;    EMT;    PI3K/Akt/mTOR;   

DOI  :  10.21037/jgo-21-310

学科分类：肿瘤学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: To explore the potential biological function of XPA (Xeroderma pigmentosum group A) in hepatic neoplasms and the underlying molecular mechanisms.Methods: Liver cells were used as experimental models to establish HCC (hepatocellular carcinoma) in vitro. Protein extractions were subjected to Western blotting to detect the proteins expression. The lentivirus transfection efficiency was confirmed by Western blot and RT-qPCR, Tunnel staining was used to detect apoptosis, and Transwell assays were used to observe cell migration and invasion. Cell proliferation was detected with colony formation and CCK-8 (cell counting kit-8) assays.Results: XPA expression was obviously lower in HCC tissue and liver cancer cell lines. XPA overexpression induced autophagy and apoptosis by increasing LC3B II/I, Beclin1, cleaved-caspase-3, and Bax expression and decreasing p62 and Bcl2 protein levels. XPA also suppressed HCC EMT (Epithelial-Mesenchymal Transition) by increasing E-cadherin and decreasing N-cadherin and vimentin protein expression. Cell proliferation, migration and invasion in vivo were significantly inhibited by the overexpression of XPA, and p-PI3K, p-Akt, and p-mTOR expression were decreased in LV-XPA cells. In general, XPA inhibited HCC by inducing autophagy and apoptosis and by modulating the expression of PI3K/Akt/mTOR proteins.Conclusions: XPA overexpression was found to suppress HCC by inducing autophagy and apoptosis and repressing EMT and proliferation. Each of these effects may be involved in modulating the PI3K/Akt/mTOR signaling pathway.

【 授权许可】

Unknown