TARBP2-mediated destabilization of Nanog overcomes sorafenib resistance in hepatocellular carcinoma

Hui Huang Lai, Chih Wei Li, Chih Chen Hong, Hung Yu Sun, Ching Feng Chiu, Da Liang Ou, Pai Sheng Chen

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24 引文 斯高帕斯(Scopus)

摘要

Hepatocellular carcinoma (HCC) is a lethal human malignancy and a leading cause of cancer-related death worldwide. Patients with HCC are often diagnosed at an advanced stage, and the prognosis is usually poor. The multikinase inhibitor sorafenib is the first-line treatment for patients with advanced HCC. However, cases of primary or acquired resistance to sorafenib have gradually increased, leading to a predicament in HCC therapy. Thus, it is critical to investigate the mechanism underlying sorafenib resistance. Transactivation response element RNA-binding protein 2 (TARBP2) is a multifaceted miRNA biogenesis factor that regulates cancer stem cell (CSC) properties. The tumorigenicity and drug resistance of cancer cells are often enhanced due to the acquisition of CSC features. However, the role of TARBP2 in sorafenib resistance in HCC remains unknown. Our results demonstrate that TARBP2 is significantly downregulated in sorafenib-resistant HCC cells. The TARBP2 protein was destabilized through autophagic–lysosomal proteolysis, thereby stabilizing the expression of the CSC marker protein Nanog, which facilitates sorafenib resistance in HCC cells. In summary, here we reveal a novel miRNA-independent role of TARBP2 in regulating sorafenib resistance in HCC cells.

原文English
頁(從 - 到)928-945
頁數18
期刊Molecular Oncology
13
發行號4
DOIs
出版狀態Published - 2019 4月

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 遺傳學
  • 腫瘤科
  • 癌症研究

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