Inhibition of SIRT7 promotes STAT1 activation and STAT1-dependent signaling in hepatocellular carcinoma

作者全名："Dong, Ling; Wei, Xufu; Yu, Le; Li, Yixin; Chen, Lixue"

作者地址："[Dong, Ling; Chen, Lixue] Chongqing Med Univ, Lab Res Ctr, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Wei, Xufu] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Yu, Le] Chongqing Univ, Sch Life Sci, Chongqing 401331, Peoples R China; [Li, Yixin] Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing 400016, Peoples R China; [Dong, Ling; Chen, Lixue] Chongqing Med Univ, Affiliated Hosp 1, Lab Res Ctr, 1st You Yi Rd, Chongqing 400016, Peoples R China"

通信作者："Dong, L; Chen, LX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Lab Res Ctr, 1st You Yi Rd, Chongqing 400016, Peoples R China."

来源：CELLULAR SIGNALLING

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001141725600001

JCR分区：Q2

影响因子：4.8

年份：2024

卷号：114

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Sirtuin 7; Hepatocellular carcinoma; Signal transducer and activator of transcription 1; Interferon signaling; Cell apoptosis

摘要："The signal transducer and activator of transcription 1 (STAT1) plays a crucial role in regulating tumor progression. However, the mechanisms governing its phosphorylation and biological functions remain incompletely understood. Here, we present compelling evidence indicating that knockdown of SIRT7 inhibits Smurf1-induced ubiquitination of STAT1, consequently impeding the proteasome pathway degradation of STAT1. This inhibition leads to increased stability of STAT1 and enhanced binding to JAK1. Importantly, SIRT7 exerts a negative regulatory effect on STAT1 activation and IFN-gamma/STAT1 signaling in hepatocellular carcinoma (HCC). Etoposide treatment not only facilitates STAT1 activation but also downregulates SIRT7 expression. Notably, knockdown of STAT1 in SIRT7-deficient cells attenuates the increase in cell apoptosis induced by Etoposide treatment. In conclusion, our data shed light on the intricate interplay between ubiquitination, STAT1, SIRT7, and Smurf1, elucidating their impact on STAT1-related signaling. These insights contribute to a more comprehensive understanding of the molecular mechanisms involved in STAT1 regulation and suggest potential avenues for the development of targeted therapies against cancer."

基金机构："National Natural Science Foundation of China [81671093, 82302923]; Natural Science Founda-tion Project of CQ CSTC [cstc2021jcyj-msxm1919]"

基金资助正文：<B>Funding</B> This work was supported by National Natural Science Foundation of China (No: 81671093 and 82302923) and by Natural Science Founda-tion Project of CQ CSTC (No: cstc2021jcyj-msxm1919) .