Long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 cooperates with enhancer of zeste homolog 2 to promote hepatocellular carcinoma development by modulating the microRNA‐22/Snail family transcriptional repressor 1 axis
Open Access
- 4 March 2020
- journal article
- research article
- Published by Wiley in Cancer Science
- Vol. 111 (5), 1582-1595
- https://doi.org/10.1111/cas.14372
Abstract
MALAT1 is an oncogenic lncRNA that has been found to promote carcinogenesis and metastasis in many tumors. However, the underlying role of MALAT1 in the progression and metastasis of hepatocellular carcinoma (HCC) remains unclear. In this study, aberrantly elevated levels of MALAT1 were detected in both HCC specimens and cell lines. We found that knockdown of MALAT1 caused retardation in proliferation, migration and invasion both in vivo and in vitro. Mechanistic investigations showed that SNAI1 is a direct target of miR‐22 and that MALAT1 modulates SNAI1 expression by acting as a competing endogenous RNA for miR‐22. Inhibition of miR‐22 restored SNAI1 expression suppressed by MALAT1 knockdown. Furthermore, MALAT1 facilitated the enrichment of EZH2 at the promoter region of miR‐22 and E‐cadherin, which was repressed by MALAT1 knockdown. MALAT1, cooperating with EZH2, positively regulated SNAI1 by repressing miR‐22 and inhibiting E‐cadherin expression, playing a vital role in epithelial to mesenchymal transition (EMT). In conclusion, our results reveal a mechanism by which MALAT1 promotes HCC progression and provides a potential target for HCC therapy.Keywords
Funding Information
- Natural Science Foundation of Hubei Province (2019CFB496)
- National Natural Science Foundation of China (81772967)
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