MicroRNA-376c-3p Facilitates Human Hepatocellular Carcinoma Progression via Repressing AT-Rich Interaction Domain 2
| Autor: | Xiaowei Chang, Song Zhai, Guoying Pan, Weiping Chang, Shuangsuo Dang, Yuan Wang, Wanli Chang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
proliferation Biology medicine.disease_cause miR-376c-3p Metastasis 03 medical and health sciences 0302 clinical medicine ARID2 microRNA medicine Gene silencing Gene knockdown Cell growth hepatocellular carcinoma medicine.disease invasion digestive system diseases 030104 developmental biology Oncology 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Carcinogenesis Liver cancer Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| Popis: | Hepatocellular carcinoma (HCC), accounting for approximately 90% of liver cancer, is the most lethal malignant tumors in the world. Large amount of evidence indicate that microRNAs (miRNAs) contribute to the tumorigenesis and progression of HCC. Among them, miR-376c-3p was recently identified as a tumor-related miRNA and is up-regulated in HBV-related HCC. But, the clinical significance of miR-376c-3p and its biological function in HCC progression are still unclear. Here, we confirmed that miR-376c-3p expression level in HCC was markedly higher than that in noncancerous tissues. Up-regulation of miR-376c-3p was detected in four different HCC cell lines. High miR-376c-3p expression correlated with poor prognostic features, such as large tumor size and venous infiltration. Follow-up data indicated that high miR-376c-3p level evidently correlated with poor clinical outcomes of HCC patients. Moreover, knockdown of miR-376c-3p repressed HCC cell growth, migration and invasion in vitro. miR-376c-3p overexpression facilitated these malignant behaviors of Bel-7402 cells. Mechanistically, miR-376c-3p posttranscriptionally repressed ARID2 expression by directly interacting with its 3'-UTR. Furthermore, an obvious negative correlation between miR-376c-3p and ARID2 mRNA expression in HCC tissues was confirmed. Notably, miR-376c-3p knockdown suppressed HCC growth and metastasis in nude mice. Gain-of-function experiments showed that ARID2 inhibited cell growth and mobility of Hep3B cells. Subsequently, ARID2 knockdown rescued miR-376c-3p silencing attenuated Hep3B cell proliferation and mobility. Our results suggest that miR-376c-3p exerts an oncogenic role in HCC progression. |
| Databáze: | OpenAIRE |
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