Tmem39b 通过抑制肝细胞癌中的铁蛋白沉积促进肿瘤进展和索拉非尼耐药。

IF 2 4区 医学 Q3 ONCOLOGY
Oncology Research Pub Date : 2024-07-17 eCollection Date: 2024-01-01 DOI:10.32604/or.2024.046170
Ming Zhuang, Xue Zhang, L U Li, Liming Wen, Jiamin Qin
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引用次数: 0

摘要

肝细胞癌(HCC)对人类健康构成重大威胁。在 HCC 化疗过程中,索拉非尼的抗药性是一个常见的重大问题,对临床治疗产生了深远影响。虽然跨膜蛋白(TMEM)家族的一些成员与 HCC 的发生和发展有关联,但 TMEM39b 与 HCC 之间的关系仍未得到探讨。这项研究发现,TMEM39b 在 HCC 中明显过表达,这与预后不良有关。随后的研究发现,RAS-选择性致死3(RSL3)诱导了HCC中明显的铁变态反应,而敲除TMEM39b的表达可显著降低其严重程度。同样,索拉非尼诱导 HCC 发生铁变态反应后,敲低 TMEM39b 的表达也会降低铁变态反应的严重程度,从而增强 HCC 对索拉非尼的耐受性。总之,我们认为 TMEM39b 可通过抑制 HCC 中的铁突变促进肿瘤进展并增强对索拉非尼的耐受性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tmem39b promotes tumor progression and sorafenib resistance by inhibiting ferroptosis in hepatocellular carcinoma.

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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来源期刊
Oncology Research
Oncology Research 医学-肿瘤学
CiteScore
4.40
自引率
0.00%
发文量
56
审稿时长
3 months
期刊介绍: Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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