LncRNA CASC9 promotes esophageal squamous cell carcinoma metastasis through upregulating LAMC2 expression by interacting with the CREB-binding protein.

作者: Yan Liang , Xuedan Chen , Yuanyuan Wu , Juan Li , Shixin Zhang

DOI: 10.1038/S41418-018-0084-9

关键词:

摘要: Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Long noncoding RNAs (lncRNAs) are thought to play a critical role in cancer development. Recently, lncRNA CASC9 was shown be dysregulated many types, but mechanisms whereby this occurs remain largely unknown. In study, we found that significantly upregulated ESCC tissues, with further analysis revealing elevated expression associated prognosis and metastasis. Furthermore, knockdown repressed migration invasion vitro metastasis nude mice vivo. A microarray mechanical experiments indicated preferentially affected gene linked ECM–integrin interactions, including LAMC2, an upstream inducer integrin pathway. We demonstrated LAMC2 consistently promoted overexpression partially compromised decrease capacity knockdowns. addition, both depletion reduced phosphorylation FAK, PI3K, Akt, which downstream effectors Moreover, reduction caused by rescued overexpression, confirming exerts pro-metastatic through LAMC2. Mechanistically, RNA pull-down RNA-binding protein immunoprecipitation (RIP) assay could bind transcriptional coactivator CREB-binding (CBP) nucleus. Chromatin (ChIP) additionally illustrated increased enrichment CBP H3K27 acetylation promoter, thereby upregulating expression. conclusion, demonstrate upregulates binding modifying histone acetylation. Our research reveals prognostic roles for ESCC, suggesting serve as biomarker target treatment.

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