TMEM43 promotes the development of hepatocellular carcinoma by activating VDAC1 through USP7 deubiquitination.

BACKGROUND: Transmembrane protein 43 ( TMEM43 ), a member of the TMEM subfamily, is encoded by a highly conserved gene and widely expressed in most species from bacteria to humans. In previous studies, TMEM43 has been found to play an important role in a variety of tumors. However, the role of TMEM43 in cancer remains unclear.

METHODS: We utilized the RNA sequencing (RNA-seq) and The Cancer Genome Atlas (TGCA) databases to explore and identify genes that may play an important role in the occurrence and development of hepatocellular carcinoma (HCC), such as TMEM43 . The role of TMEM43 in HCC was explored through Cell Counting Kit-8 (CCK-8) cloning, flow cytometry, and Transwell experiments. The regulatory relationship between TMEM43 and voltage-dependent anion channel 1 ( VDAC1 ) was investigated through coimmunoprecipitation (co-IP) and western blot (WB) experiments. WB was used to study the deubiquitination effect of ubiquitin-specific protease 7 ( USP7 ) on TMEM43 .

RESULTS: In this study, we utilized the RNA-seq and TGCA databases to mine data and found that TMEM43 is highly expressed in HCC. The absence of TMEM43 in cancer cells was shown to inhibit tumor development. Further research detected an important regulatory relationship between TMEM43 and VDAC1 . In addition, we found that USP7 affected the progression of HCC by regulating the ubiquitination level of TMEM43 through deubiquitination.

CONCLUSIONS: Our study demonstrated that USP7 participates in the growth of HCC tumors through TMEM43/VDAC1 .Our results suggest that USP7/TMEM43/VDAC1 may have predictive value and represent a new treatment strategy for HCC.