KHDRBS3 accelerates glycolysis and promotes malignancy of hepatocellular carcinoma via upregulating 14-3-3ζ

Cancer Cell International

Research

Chunhui Wang¹  Xiaobin Liu¹  Yufu Tang¹  Longfei Li¹  Wenping Zhou¹  Mingda Zhao²  Yibing Zhang³ 

[1] Department of Hepatobiliary Surgery, General Hospital of Northern Theater Command, 83#, Wenhua Road, Shenyang, Liaoning, China;Department of Hepatobiliary Surgery, General Hospital of Northern Theater Command, 83#, Wenhua Road, Shenyang, Liaoning, China;Dalian Medical University, Dalian, Liaoning, China;Department of Medical Affairs, General Hospital of Northern Theater Command, Shenyang, Liaoning, China;

关键词: Hepatocellular carcinoma;    KHDRBS3;    14-3-3ζ;    Glycolysis;    Doxorubicin resistance;   

DOI  :  10.1186/s12935-023-03085-4

 received in 2023-05-06, accepted in 2023-09-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPrimary hepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality. KH domain-containing, RNA-binding signal transduction-associated protein 3 (KHDRBS3) is an RNA-binding protein that is aberrantly expressed in multiple tumors; however, its expression and biological function in HCC have not been reported.MethodsKHDRBS3 knockdown and overexpression were performed using the lentiviral vector system to investigate the effects of KHDRBS3 on cell proliferation, apoptosis, chemoresistance, and glycolysis. Murine xenograft tumor models were constructed to study the role of KHDRBS3 on tumor growth in vivo. Furthermore, RNA-Pull Down and RNA immunoprecipitation were utilized to explore the interaction between KHDRBS3 and 14-3-3ζ, a phosphopeptide-binding molecule encoded by YWHAZ.ResultsKHDRBS3 was highly expressed in human HCC tissues and predicted the poor prognosis of patients with HCC. Knockdown of KHDRBS3 exhibited a carcinostatic effect in HCC and impeded proliferation and tumor growth, reduced glycolysis, enhanced cell sensitivity to doxorubicin, and induced apoptosis. On the contrary, forced expression of KHDRBS3 expedited the malignant biological behaviors of HCC cells. The expression of KHDRBS3 was positively correlated with the expression of 14-3-3ζ. RNA immunoprecipitation and RNA pull-down assays demonstrated that KHDRBS3 bound to YWHAZ. We further confirmed that 14-3-3ζ silencing significantly reversed the promotion of proliferation and glycolysis and the inhibition of apoptosis caused by KHDRBS3 overexpression.ConclusionsOur findings suggest that KHDRBS3 promotes glycolysis and malignant progression of HCC through upregulating 14-3-3ζ expression, providing a possible target for HCC therapy.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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