A novel role of TCAIM: suppressing renal carcinoma growth and enhancing its sensitivity to sunitinib. (11th March 2022)

• Record Type: Journal Article
• Authors: Ye, Zhuo; Ren, Chuanchuan; Wang, Qingwei; Wang, Yan
• Is Part Of: FEBS journal. Volume 289:Number 17(2022)
• Page Start: 5259
• Page End: 5278
• Publication Date: 2022-03-11
• Subjects: apoptosis -- cell cycle -- renal carcinoma -- T cell activation inhibitor mitochondrial -- vitamin D receptor; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.16417
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Renal carcinoma is a common malignancy for which the underlying molecular mechanisms warrant further investigation. T cell activation inhibitor mitochondrial (TCAIM), a mitochondrial protein, was found to be expressed to a low extent in renal carcinoma specimens. However, its role in carcinomas remains unclear. In the present study, the role of TCAIM in renal carcinoma was explored through loss‐of‐function and gain‐of‐function experiments. Here, we showed that TCAIM delayed the growth of renal carcinoma cells both in vitro and in vivo by modulating their cell cycle progress. Additionally, TCAIM also enhanced their sensitivity to sunitinib by aggravating apoptosis. Furthermore, TCAIM also decreased the adhesion and migration of renal carcinoma cells. Moreover, the transcription of TCAIM was regulated by vitamin D receptor, which acts as a transcriptional factor. To identify the pathways regulated by TCAIM, 425 unique proteins bound to TCAIM were pulled down through co‐immunoprecipitation and analyzed by mass spectrometry followed by Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis. In summary, the present study reveals a tumor‐suppressor role of TCAIM in renal carcinoma cells, as well as its upstream regulation and downstream potential mechanisms. Our study provides theoretical bases and novel insights with respect to the development of new therapeutic strategies for the treatment of renal carcinoma. Abstract : Expression levels of T cell activation inhibitor mitochondrial (TCAIM) are decreased in renal carcinoma. Here, we showed that TCAIM delays the growth of renal carcinoma cells by modulating progression through the cell cycle and enhances their sensitivity to sunitinib by aggravating apoptosis. Furthermore, TCAIM decreases the adhesion and migration of renal carcinoma cells. Moreover, the transcription of TCAIM is regulated by vitamin D receptor. The downstream pathways regulated by TCAIM are also identified.