Journal of Cell Biology (JCB)
Journal of Cell Biology (JCB)
5 years ago

Knockdown of long non-coding RNA MALAT1 inhibits growth and motility of human hepatoma cells via modulation of miR-195

Knockdown of long non-coding RNA MALAT1 inhibits growth and motility of human hepatoma cells via modulation of miR-195
Xiaorong Feng, Dingli Liu, Jinke Pang, Xie Weng, Yabing Guo, Yun Zhu
The metastasis-associated lung adenocarcinoma transcription 1 (Malat1) is a long non-coding RNA (lncRNA), exerts oncogenic role in multiple cancers, including hepatocellular carcinoma (HCC). This study was aimed to investigate its posttranscriptional regulation in HCC cells. RT-PCR was performed to monitor the expression levels of Malat1 in normal liver and HCC cell lines. The expression of Malat1, microRNA (miR)-195, and epidermal growth factor receptor (EGFR) in HepG2 and MHCC97 cells was respectively or synchronously altered by transfection. Then the changes in cell viability, apoptotic cell rate, cell cycle distribution, migration, and invasion were respectively assessed. As a result, we found that Malat1 was highly expressed in HCC cell lines when compared to normal liver cells. Malat1 silence suppressed HCC cells viability, migration and invasion, induced apoptosis, and arrested more cells in G0/G1 phase. Malat1 acted as a circular endogenous RNA (ceRNA) for miR-195. Malat1 silence could not suppress HCC cell growth and motility when miR-195 was knocked down. EGFR was a direct target of miR-195. miR-195 overexpression could not suppress HCC cell growth and motility when the 3′UTR site of EGFR was overexpressed. Furthermore, Malat1 silence blocked the activation of PI3K/AKT and JAK/STAT pathways, while EGFR overexpression activated them. Our study demonstrates Malat1-miR-195-EGFR axis plays a critical role in HCC cells which provided a better understanding of Malat1 in HCC. Malat1 silencing inhibits HCC cells growth and motility. MiR-195 involves in Malat1-mediaed carcinogenesis and plays an antitumor role via targeting the 3′UTR of epidermal growth factor receptor (EGFR). Malat1-miR-195-EGFR axis plays a critical role in HCC cells.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26297

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