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

研究成果: 雜誌貢獻文章

1 引文 (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.
原文英語
期刊Molecular Oncology
DOIs
出版狀態打印前電子出版 - 一月 18 2019

指紋

RNA-Binding Proteins
Response Elements
Transcriptional Activation
Hepatocellular Carcinoma
Neoplastic Stem Cells
MicroRNAs
Neoplasms
sorafenib
Drug Resistance
Proteolysis
Down-Regulation
Therapeutics

引用此文

TARBP2-mediated destabilization of Nanog overcomes sorafenib resistance in hepatocellular carcinoma. / Lai, Hui-Huang; Li, Chih-Wei; Hong, Chih-Chen; Sun, Hung-Yu; Chiu, Ching-Feng; Ou, Da-Liang; Chen, Pai-Sheng.

於: Molecular Oncology, 18.01.2019.

研究成果: 雜誌貢獻文章

Lai, Hui-Huang ; Li, Chih-Wei ; Hong, Chih-Chen ; Sun, Hung-Yu ; Chiu, Ching-Feng ; Ou, Da-Liang ; Chen, Pai-Sheng. / TARBP2-mediated destabilization of Nanog overcomes sorafenib resistance in hepatocellular carcinoma. 於: Molecular Oncology. 2019.
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abstract = "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.",
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AU - Lai, Hui-Huang

AU - Li, Chih-Wei

AU - Hong, Chih-Chen

AU - Sun, Hung-Yu

AU - Chiu, Ching-Feng

AU - Ou, Da-Liang

AU - Chen, Pai-Sheng

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N2 - 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.

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