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Front Pharmacol. 2019 Jan 10;9:1565. doi: 10.3389/fphar.2018.01565. eCollection 2018.

MicroRNA-181a Functions as an Oncogene in Gastric Cancer by Targeting Caprin-1.

Author information

1
Department of Pathology, Weifang Medical University, Weifang, China.
2
Department of Histology and Embryology, Weifang Medical University, Weifang, China.
3
Neurological Disorders and Regenerative Repair Key Laboratory, Weifang Medical University, Weifang, China.
4
Department of Bioscience and Technology, Weifang Medical University, Weifang, China.
5
Department of Joint Surgery, Affiliated Hospital of Weifang Medical University, Weifang, China.

Abstract

MicroRNA-181a (miRNA-181a) is a multifaceted miRNA implicated in various cellular processes, particularly in cell fate determination and cellular invasion. It is frequently expressed aberrantly in human tumors and shows opposing functions in different types of cancers. In this study, we found that miRNA-181a is overexpressed in Gastric cancer (GC) tissues. Clinical and pathological analyses revealed that the expression of miRNA-181a is correlated with tumor size, lymph node metastasis, distant metastasis, and TNM stage. Kaplan-Meier analysis indicated that overexpression of miRNA-181a is associated with poor overall survival of patients with GC. Moreover, miRNA-181a is overexpressed in GC cells, and downregulation of miRNA-181a induced cell apoptosis and suppressed the proliferation, invasion, and metastasis of GC cells both in vitro and in vivo. Target prediction and luciferase reporter assay showed that caprin-1 was a direct target of miRNA-181a. Downregulation of caprin-1 expression resulted in a converse change with miRNA-181a in GC. Spearman's correlation test confirmed that the expression of miRNA-181a expression was inversely correlated with that of caprin-1 in GC cells. Furthermore, the expression of caprin-1 increased after downregulation of miRNA-181a in the GC cells. Caprin-1 siRNA can rescue the oncogenic effect of miRNA-181a on GC cell proliferation, apoptosis, migration, and invasion. These findings suggest that miRNA-181a directly inhibits caprin-1 and promotes GC development. miRNA-181a could be a target for anticancer drug development.

KEYWORDS:

caprin-1; gastric cancer; metastasis; miRNA-181a; oncogene

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