LOC441178 Overexpression Inhibits the Proliferation and Migration of Esophageal Carcinoma Cells via Methylation of miR-182

Abstract

Weitao Hu,* Zongchi Chen,* Jiangmu Chen, Daxing Cai, Congjie Chen, Taiyong Fang Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Taiyong FangDepartment of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, 34 North Zhongshan Road, Licheng District, Quanzhou, Fujian 362000, People’s Republic of ChinaEmail [email protected]: Long noncoding RNAs (lncRNAs) have been shown to play an important role in the development and progression of esophageal carcinoma (EC). Recently, lncRNA LOC441178 was shown to be dysregulated in many cancer types; however, the role of LOC441178 in EC remains unclear.Materials and Methods: Flow cytometry, transwell and wound healing assays were used to measure the apoptosis and migration in esophageal squamous cell carcinoma (ESCC) cells. RT-qPCR was used to detect the level of miR-182 in LOC441178-overexpressed EC cells. In addition, DNA methylation status of miR-182 promoter in LOC441178-overexpressed ESCC cells was detected by methylation-specific PCR (MSP) and bisulfite sequencing PCR.Results: In this study, we found that LOC441178 negatively regulated miR-182 expression in ESCC cells. In addition, overexpression of LOC441178 inhibited the proliferation and migration and induced apoptosis in ESCC cells via downregulation of miR-182. Moreover, overexpression of LOC441178 markedly inhibited the phosphorylation of Akt and phosphorylation FOXO3a and increased the expression of FOXO3a in ESCC cells via downregulation of miR-182. Mechanistically, LOC441178 overexpression epigenetically suppressed miR-182 expression via DNA methylation. In vivo experiments revealed that overexpression of LOC441178 inhibited ESCC tumor growth in mouse xenograft model.Conclusion: Collectively, our data suggested that LOC441178 overexpression epigenetically inhibited tumorigenesis of ESCC via DNA methylation of miR-182. These data indicated that the LOC441178/miR-182 axis might represent a novel therapeutic option for the treatment of ESCC.Keywords: esophageal carcinoma, lncRNA LOC441178, miR-182, DNA methylation

Keywords

• esophageal carcinoma
• lncrna loc441178
• mir-182
• dna methylation.