UHRF2 promotes the malignancy of hepatocellular carcinoma by PARP1 mediated autophagy

作者全名："Zhang, Yiqi; Wu, Kejia; Liu, Yuxin; Sun, Shuangling; Shao, Yue; Li, Qingxiu; Sui, Xinying; Duan, Changzhu"

作者地址："[Zhang, Yiqi; Wu, Kejia; Liu, Yuxin; Li, Qingxiu; Sui, Xinying; Duan, Changzhu] Chongqing Med Univ, Ctr Mol Med & Oncol Res, Dept Cell Biol & Genet, Chongqing 400016, Peoples R China; [Sun, Shuangling] Chongqing Med & Pharmaceut Coll, Dept Biochem, Chongqing 400016, Peoples R China; [Shao, Yue] Chongqing Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Chongqing 400016, Peoples R China"

通信作者："Duan, CZ (通讯作者)，Chongqing Med Univ, Ctr Mol Med & Oncol Res, Dept Cell Biol & Genet, Chongqing 400016, Peoples R China."

来源：CELLULAR SIGNALLING

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001026650200001

JCR分区：Q2

影响因子：4.4

年份：2023

卷号：109

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：HCC; UHRF2; Autophagy; PARP1; Pathway; PRDX1

摘要："Autophagy have critical implications in the proliferation and metastasis of HCC. In the current study, we aimed to explore the underlying mechanisms of UHRF2 regulates HCC cells autophagy and HCC progression. We initially determined the relationship between UHRF2 and HCC autophagy, oncogenicity and patient survival through GSEA database and TCGA database. We mainly investigated the effect of UHRF2 on HCC development and autophagy through western blot, electron microscopy, and immunofluorescence. Functionally, UHRF2 was positively involved in the autophagy activation. Overexpression of UHRF2 reduced apoptosis in HCC cells, and promoted the malignancy phenotype of HCC both in vitro and in vivo. Mechanistically, PRDX1 bound to UHRF2 and upregulated its protein expression to facilitate the biological function of UHRF2 in HCC. Meanwhile, UHRF2 bound to autophagy-related protein PARP1 and upregulated PARP1 protein level. The results showed that UHRF2 promoted autophagy and contributed to the malignant phenotype of HCC by regulating PARP1 protein level. In summary, a novel interaction between PRDX1, UHRF2, and PARP1 was revealed, suggesting that UHRF2 could inspire a potential biomarker and potential therapeutic target for HCC."

基金机构：Chongqing Scientific Research and Innovation Project [CYS21213]; Natural Science Foundation of China [81772178]

基金资助正文：Funding The research was funded by the Chongqing Scientific Research and Innovation Project (CYS21213) and Natural Science Foundation of China (No. 81772178) . The authors appreciate their assistance.