MiR-638 regulates gastric cardia adenocarcinoma cell proliferation, apoptosis, migration and invasion by targeting MACC1

 Chang-Jiang Wei, Zhi-Wei Zhang, Jia-Hao Lu, Yi-Ming Mao

Abstract:

Gastric cardia adenocarcinoma (GCA) is one of the most common types of cancer and the incidence is increasing globally. MicroRNAs (miRNAs) have been reported to play critical roles in the progression of GCA. However, the exact role of miR-638 in GCA and its underlying mechanism remain largely unknown. The expression levels of miR-638 and metastasis-associated in colon cancer 1 (MACC1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8) assay, flow cytometry and transwell assay, respectively. Western blot analysis was performed to determine the protein levels of cleaved-caspase 3 (C-caspase 3) and MACC1. The possible binding sites of miR-638 and MACC1 were predicted by TargetScan online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft model was established to investigate the roles of MACC1 in GCA in vivo. The expression of miR-638 was evidently reduced and MACC1 expression was obviously enhanced in GCA tissues and cells. Overexpression of miR-638 or knockdown of MACC1 inhibited cell proliferation, migration and invasion but increased apoptosis in GCA cells. Moreover, MACC1 was a direct target of miR-638 and its upregulation attenuated the inhibitory effect of miR-638 overexpression on the progression of GCA. In addition, overexpression of miR-638 significantly decreased tumor growth by downregulating MACCI in vivo. In conclusion, miR-638 overexpression suppressed cell proliferation, migration and invasion but induced cell apoptosis by targeting MACC1 in GCA cells, providing a potential therapeutic strategy for the treatment of GCA.