Year-end Sale % OFF 
Abstract
It has been proved that TRAFs family proteins played malfunctioning roles in the development of human cancers. TRAF7 is the last one of TRAFs family proteins to be found, which was demonstrated to be involved in a serious of cancers development. In this study, we systematically investigated the molecular mechanisms of TRAF7 in facilitating hepatocellular carcinoma (HCC). We discovered that TRAF7 was overexpressed in tumor tissues and the increased TRAF7 expression was closely associated with tumor size, histologic grade, TNM stage and poor prognostication. TRAF7 overexpression repressed cell apoptosis and promoted cell proliferation, invasion and migration, whereas knockdown of TRAF7 in HCC cells had totally opposite effects. Besides, we identified the interaction between TRAF7 and P53 in HCC and demonstrated that TRAF7 promoted ubiquitin-proteasome mediated degradation of P53 at K48 site. The rescue assays further proved that the function of TRAF7 in inhibiting apoptosis and promoting tumor development was depended on P53 in HCC. Overall, this work identified that TARF7 promoted tumorigenesis by targeted degradation P53 for ubiquitin-mediated proteasome pathway. Targeting the TRAF7-P53 axis may provide new insights in the pathogenesis of HCC, and pave the way for developing novel strategies for HCC prevention and treatment.
Highlights
Hepatocellular carcinoma (HCC) is the fourth leading causes of cancer-related death and the most common type of primary hepatic neoplasm
TRAF7 was increased in HCC tumor tissues To investigate the role of TRAF7 in HCC, we firstly examined the TRAF7 expression profile by Quantitative real-time PCR (qRT-PCR) and Western Blot assays
The results indicated that the mRNA levels of TRAF7 in tumor tissues were upregulated compared with adjacent non-tumor tissues (Fig. 1A)
Summary
Hepatocellular carcinoma (HCC) is the fourth leading causes of cancer-related death and the most common type of primary hepatic neoplasm. More than 80 thousand patients were diagnosed with HCC and more than 70 thousand patients with HCC died during 2018 [1]. A variety of pathogenesis have been reported to be associated with HCC, among which Hepatitis B virus and Hepatitis C virus infection, alcohol-abusing, and nonalcohol fatty liver disease are the major factors for HCC occurrence [2]. How HCC happens and its underling mechanisms remain poorly understood. Plenty kinds of treatment methods such as hepatectomy and targeted drug therapy have been applied for HCC, the patients’ prognostication are still very poor [3]. There is an urgent need to identify new therapeutic targets and drugs for HCC treatment
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
