Open AccessTARBP 2‐mediated destabilization of Nanog overcomes sorafenib resistance in hepatocellular carcinoma
Author(s) -
Lai HuiHuang,
Li ChihWei,
Hong ChihChen,
Sun HungYu,
Chiu ChingFeng,
Ou DaLiang,
Chen PaiSheng
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12449
Subject(s) - sorafenib , hepatocellular carcinoma , cancer research , homeobox protein nanog , medicine , cancer , transactivation , cancer stem cell , oncology , biology , transcription factor , biochemistry , embryonic stem cell , induced pluripotent stem cell , gene
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 mi RNA 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 TARBP 2 in sorafenib resistance in HCC remains unknown. Our results demonstrate that TARBP 2 is significantly downregulated in sorafenib‐resistant HCC cells. The TARBP 2 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 mi RNA ‐independent role of TARBP 2 in regulating sorafenib resistance in HCC cells.