Open AccessLong 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
Author(s) -
Chen Shaofei,
Wang Guobin,
Tao Kaixiong,
Cai Kailin,
Wu Ke,
Ye Lin,
Bai Jie,
Yin Yuping,
Wang Jiliang,
Shuai Xiaoming,
Gao Jinbo,
Pu Jiarui,
Li Hang
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14372
Subject(s) - gene knockdown , snai1 , malat1 , cancer research , biology , long non coding rna , microrna , competing endogenous rna , carcinogenesis , metastasis , rna interference , repressor , hotair , epithelial–mesenchymal transition , rna , gene expression , gene , cancer , genetics
Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic long noncoding RNA 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 Snail family transcriptional repressor 1 (SNAI1) is a direct target of microRNA (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 enhancer of zeste homolog 2 (EZH2) at the promoter region of miR‐22 and E‐cadherin, which was repressed by MALAT1 knockdown. Cooperating with EZH2, MALAT1 positively regulated SNAI1 by repressing miR‐22 and inhibiting E‐cadherin expression, playing a vital role in epithelial to mesenchymal transition. In conclusion, our results reveal a mechanism by which MALAT1 promotes HCC progression and provides a potential target for HCC therapy.