miR-194 inhibits liver cancer stem cell expansion by regulating RAC1 pathway
| Autor: | Jun Chen, Xiao-Lu Lin, Cong Zhuangzhi, Yong-Jie Zhang, Rong-zheng Ran, Tan Weifeng, Hai Zhang, Guoqing Zhang, Fan Mingming, Longjiu Cui |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
rac1 GTP-Binding Protein
0301 basic medicine Carcinoma Hepatocellular Sorafenib treatment Down-Regulation RAC1 Mice SCID Drug resistance Biology medicine.disease_cause Mice 03 medical and health sciences 0302 clinical medicine Mice Inbred NOD Cell Line Tumor Biomarkers Tumor medicine Animals Functional studies Cell Self Renewal Cells Cultured Liver Neoplasms Cell Biology medicine.disease MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Hepatocellular carcinoma Neoplastic Stem Cells Cancer research Stem cell Liver cancer Carcinogenesis |
| Zdroj: | Experimental Cell Research. 378:66-75 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2019.03.007 |
| Popis: | Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver CSCs remains unclear. Herein, we observed low expression of miR-194 in chemoresistant HCC cells. A remarkable decrease of miR-194 was detected in EpCAM or CD133-positive liver CSCs and CSC-enriched hepatoma spheres. Interference miR-194 facilitated liver CSCs expansion by enhancing the self-renewal of liver CSCs. While up-regulating miR-194 inhibited liver CSCs expansion by suppressing the self-renewal of liver CSCs. Furthermore, hepatoma cells with miR-194 overexpression performed more sensitivity to sorafenib treatment. Mechanistically, functional studies found that Ras-related C3 botulinum toxin substrate 1 (RAC1) was a direct target of miR-194. Overexpression of miR-194 inhibited the expression of RAC1 in liver CSCs. Special RAC1 siRNA diminished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-194 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-194-inhibited liver CSCs expansion. More importantly, downregulated expression of miR-194 was a predictor of poor prognosis of HCC patients. |
| Databáze: | OpenAIRE |
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