Long noncoding RNA MALAT1 promotes malignant development of esophageal squamous cell carcinoma by targeting β-catenin via Ezh2.
Long noncoding RNA MALAT1 promotes malignant development of esophageal squamous cell carcinoma by targeting β-catenin via Ezh2.
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DOI：
10.18632/oncotarget.8257
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发表时间：
2016-05-03
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Wang W;Zhu Y;Li S;Chen X;Jiang G;Shen Z;Qiao Y;Wang L;Zheng P;Zhang Y
有证据表明，lncrna参与包括食管鳞状细胞癌（ESCC）在内的多种癌症的发生和发展。采用qRT-PCR技术，研究了106对ESCC组织及其邻近非癌组织中lncRNA MALAT1的异常表达。分别构建下调的MALAT1和Ezh2过表达质粒，分析β-catenin、Lin28和Ezh2基因的表达情况。我们发现MALAT1在人ESCC组织中表达水平较高（P=0.0011），且与WHO分级（P=0.0395、P=0.0331）、淋巴结转移（P=0.0213）、预后（P=0.0294）密切相关。在体外实验中，沉默MALAT1表达抑制食管癌细胞的增殖、迁移和肿瘤球的形成，同时增加细胞凋亡。MALAT1的下调降低了β-catenin、Lin28和Ezh2基因的表达，而过表达Ezh2联合MALAT1的下调完全逆转了si-MALAT1介导的食管癌细胞中β-catenin和Lin28的抑制。动物实验表明，敲低MALAT1可减少肿瘤形成，提高生存率。MALAT1促进ESCC的发生和进展，提示抑制MALAT1可能是治疗ESCC的潜在靶点。
Evidences have shown that lncRNAs involve in the initiation and progression of various cancers including esophageal squamous cell carcinoma (ESCC). The aberrant expression of lncRNA MALAT1 was investigated in 106 paired ESCC tissues and adjacent non-cancerous tissues by qRT-PCR. Down-regulated MALAT1 and Ezh2 over-expression plasmid were constructed respectively to analyze the expression of β-catenin, Lin28 and Ezh2 genes. We found that the MALAT1 expression level was higher in human ESCC tissues (P=0.0011), which was closely correlated with WHO grade (P=0.0395, P=0.0331), lymph node metastasis (P=0.0213) and prognosis (P=0.0294). Silencing of MALAT1 expression inhibited cell proliferation, migration and tumor sphere formation, while increasing cell apoptosis of esophageal cancer in vitro. Down-regulation of MALAT1 decreased the expression of β-catenin, Lin28 and Ezh2 genes, while over-expressed Ezh2 combined with MALAT1 down-regulation completely reversed the si-MALAT1-mediated repression of β-catenin and Lin28 in esophageal cancer cells. Animal experiments showed that knockdown of MALAT1 decreased tumor formation and improved survival. MALAT1 promotes the initiation and progression of ESCC, suggesting that inhibition of MALAT1 might be a potential target for treatment of ESCC.
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