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Long noncoding RNA ADAMTS9‐AS2 suppresses the progression of esophageal cancer by mediating CDH3 promoter methylation
Author(s) -
Liu Donglei,
Wu Kai,
Yang Yang,
Zhu Dengyan,
Zhang Chunyang,
Zhao Song
Publication year - 2020
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23126
Subject(s) - biology , esophageal cancer , methylation , cancer research , in vivo , dnmt1 , long non coding rna , dna methylation , methyltransferase , microbiology and biotechnology , downregulation and upregulation , cancer , gene expression , gene , biochemistry , genetics
Long noncoding RNAs (lncRNAs) have been implicated in the biology of esophageal cancer via mRNA degradation or translational inhibition. CDH3 is also aberrantly expressed in numerous cancers. This study was conducted with the hypothesis that ADAMTS9‐AS2 or CDH3 methylation plays a role in esophageal cancer cell activity and in vivo development. Firstly, mRNA levels of ADAMTS9‐AS2 and CDH3 in esophageal cancer tissues and cells were detected by reverse‐transcription quantitative polymerase chain reaction. Afterward, esophageal cancer OE21 cells were treated with overexpression of ADAMTS9‐AS2, siRNA against ADAMTS9‐AS2, overexpression of CDH3 and demethylating agent 5‐aza‐dc. The biological functions of esophageal cancer OE21 cells were assayed to define the regulatory mechanisms of ADAMTS9‐AS2 in esophageal cancer. The interactions among ADAMTS9‐AS2, DNMT1/DNMT3 (A/B) and CDH3 were detected by MSP, RNA pull‐down, RIP, and ChIP assays. The in vitro findings were reproduced in nude mice to explore the role of ADAMTS9‐AS2 in the development of esophageal cancer in vivo. Esophageal cancers expressed low levels of ADAMTS9‐AS2 and high levels of CDH3. Methylation of CDH3 promoter was induced by ADAMTS9‐AS2 via DNMT1/DNMT3 (A/B). Furthermore, proliferation, invasion, and migration of esophageal cancer cells were inhibited by ADAMTS9‐AS2 via downregulation of CDH3. Suppressed esophageal cancer development in vivo was also detected after ADAMTS9‐AS2 overexpression. Overexpressed ADAMTS9‐AS2 aids in the suppression of esophageal cancer development, which is achieved via inducing CDH3 promoter methylation.