Open Access

ARTICLE

Tmem39b promotes tumor progression and sorafenib resistance by inhibiting ferroptosis in hepatocellular carcinoma

by MING ZHUANG, XUE ZHANG, LU LI, LIMING WEN, JIAMIN QIN^*

Department of Gastroenterology, Sichuan Mianyang 404 Hospital, Mianyang, 621000, China

* Corresponding Author: JIAMIN QIN. Email:

Oncology Research 2024, 32(8), 1347-1357. https://doi.org/10.32604/or.2024.046170

Received 21 September 2023; Accepted 23 February 2024; Issue published 17 July 2024

Abstract

Hepatocellular carcinoma (HCC) poses a significant threat to human health. Resistance to sorafenib in the chemotherapy of HCC is a common and significant issue that profoundly impacts clinical treatment. While several members of the transmembrane (TMEM) protein family have been implicated in the occurrence and progression of HCC, the association between TMEM39b and HCC remains unexplored. This study revealed a significant overexpression of TMEM39b in HCC, which correlated with a poor prognosis. Subsequent investigation revealed that RAS-selective lethal 3 (RSL3) induced pronounced ferroptosis in HCC, and knocking down the expression of TMEM39b significantly decreased its severity. Similarly, following the induction of ferroptosis in HCC by sorafenib, knocking down the expression of TMEM39b also decreased the severity of ferroptosis, enhancing HCC tolerance to sorafenib. In conclusion, we propose that TMEM39b promotes tumor progression and resistance to sorafenib by inhibiting ferroptosis in HCC.

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Keywords

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