Department of Gastroenterology, Sichuan Mianyang 404 Hospital, Mianyang, 621000, China.
Oncol Res. 2024 Jul 17;32(8):1347-1357. doi: 10.32604/or.2024.046170. eCollection 2024.
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.
肝细胞癌（HCC）对人类健康构成重大威胁。HCC 化疗中索拉非尼耐药是一个常见且重要的问题，对临床治疗有深远影响。尽管跨膜（TMEM）蛋白家族的几个成员与 HCC 的发生和进展有关，但 TMEM39b 与 HCC 之间的关联仍未得到探索。本研究显示 TMEM39b 在 HCC 中显著过表达，与预后不良相关。进一步的研究表明，RAS 选择性致死 3（RSL3）在 HCC 中诱导明显的铁死亡，敲低 TMEM39b 的表达显著降低其严重程度。同样，索拉非尼诱导 HCC 发生铁死亡后，敲低 TMEM39b 的表达也降低了铁死亡的严重程度，增强了 HCC 对索拉非尼的耐受性。总之，我们提出 TMEM39b 通过抑制 HCC 中的铁死亡促进肿瘤进展和对索拉非尼的耐药性。
