https://scholars.lib.ntu.edu.tw/handle/123456789/506562
標題: | TARBP2-mediated destabilization of Nanog overcomes sorafenib resistance in hepatocellular carcinoma | 作者: | Lai, Hui-Huang Li, Chih-Wei Hong, Chih-Chen Sun, Hung-Yu Chiu, Ching-Feng DA-LIANG OU Chen, Pai-Sheng |
關鍵字: | Nanog; TARBP2; cancer stem cells; hepatocellular carcinoma; miRNA; sorafenib resistance | 公開日期: | 2019 | 出版社: | WILEY | 卷: | 13 | 期: | 4 | 起(迄)頁: | 928 | 來源出版物: | Molecular oncology | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/506562 | ISSN: | 1574-7891 | DOI: | 10.1002/1878-0261.12449 | SDG/關鍵字: | alpha tubulin; autophagy related protein 5; cisplatin; messenger RNA; microRNA; octamer transcription factor 4; paclitaxel; proteasome; sorafenib; tamoxifen; transactivation response element RNA binding protein 2; transcription factor NANOG; transcription factor Sox2; ubiquitin; unclassified drug; microRNA; NANOG protein, human; RNA binding protein; sorafenib; trans-activation responsive RNA-binding protein; transcription factor NANOG; Article; bioinformatics; cancer prognosis; cancer stem cell; cancer survival; clinical outcome; down regulation; Huh-7 cell line; human; human cell; liver cell carcinoma; lysosome; priority journal; protein degradation; protein expression; real time polymerase chain reaction; transactivation; tumor gene; Western blotting; animal; autophagy; Bagg albino mouse; biological model; drug effect; drug resistance; gene expression regulation; genetics; liver cell carcinoma; liver tumor; male; metabolism; pathology; protein stability; treatment outcome; tumor cell line; Animals; Autophagy; Carcinoma, Hepatocellular; Cell Line, Tumor; Down-Regulation; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Lysosomes; Male; Mice, Inbred BALB C; MicroRNAs; Models, Biological; Nanog Homeobox Protein; Protein Stability; RNA-Binding Proteins; Sorafenib; Treatment Outcome |
顯示於: | 腫瘤醫學研究所 |
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