國家衛生研究院 NHRI:Item 3990099045/11617
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    题名: TARBP2-mediated destabilization of Nanog overcomes sorafenib resistance in hepatocellular carcinoma
    作者: Lai, HH;Li, CW;Hong, CC;Sun, HY;Chiu, CF;Ou, DL;Chen, PS
    贡献者: Institute of Molecular and Genomic Medicine
    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 (SR) 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.
    日期: 2019-04
    關聯: Molecular Oncology. 2019 Apr;13(4):928-945.
    Link to: http://dx.doi.org/10.1002/1878-0261.12449
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1574-7891&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000462913100016
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85062391008
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