期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 17, 期 12, 页码 3133-3144出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.62393
关键词
HCC; MTX1; sorafenib; autophagy; CISD1
资金
- National Natural Science Foundation of China [81772568]
- Outstanding Clinical Discipline Project of Shanghai Pudong [PWYgy201802]
The study identified Metaxin 1 (MTX1) as a key regulator of sorafenib resistance in hepatocellular carcinoma (HCC), with MTX1 overexpression promoting cell proliferation and reducing apoptosis upon sorafenib treatment by inducing autophagy through interaction with and inhibition of CISD1. High MTX1 expression was associated with poor outcomes in HCC patients receiving sorafenib treatment.
Sorafenib is the standard first-line drug for the treatment of advanced hepatocellular carcinoma (HCC), however, its therapeutic efficacy is not satisfactory due to primary or secondary resistance of HCC cells. In the present study, we identified Metaxin 1 (MTX1) as a new regulator of sorafenib resistance in HCC through genome-scale CRISPR activation (CRISPRa) screening. We found that MTX1 was frequently upregulated in HCC tissues and overexpression of MTX1 promoted HCC cell proliferation in vitro and in vivo. As well, MTX1 overexpression increased cell growth rate and decreased cell apoptosis upon sorafenib treatment. Consistently, the resistance induced by MTX1 was also observed in subcutaneous xenograft tumor model. Clinically, high expression of MTX1 was closely related with poor outcomes in HCC patients who received sorafenib treatment. Mechanistically, overexpression of MTX1 could promote HCC cell autophagy via interacting with and inhibiting CDGSH iron sulfur domain 1 (CISD1), an autophagy negative regulator. Taken together, our findings suggest that MTX1 is upregulated in HCC and contributes to sorafenib resistance via a possible mechanism involving CISD1 mediated autophagy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据