MicroRNA-143 suppresses the proliferation and metastasis of human gastric cancer cells via modulation of STAT3 expression.

Abstract

Accumulating evidences suggest that miRNAs may prove essential therapeutic targets for the treatment of cancer. Herein, the role and therapeutic implications of miRNA-143 was investigated in gastric cancer. The results revealed miRNA-143 to be aberrantly downregulated in gastric cancer cell lines. Ectopic expression of miRNA-143 resulted in a significant (<i>P</i><0.05) inhibition of AGS gastric cancer cell proliferation suggestive of the tumor suppressive role of miRNA-143. The inhibition of AGS cell proliferation was mainly via activation of apoptotic cell death as evident from the AO/EB and annexin V/PI staining. Additionally, miR-143 overexpression also caused a significant (<i>P</i><0.05) decline in the migration and invasion of AGS cells. TargetScan analysis and the dual luciferase assay revealed STAT3 to be the potential target of miRNA-143 in AGS cells. Analysis of STAT3 expression in gastric cancer cell lines showed upto 3.5 fold upregulation of STAT3. However, miRNA-143 overexpression resulted in considerable downregulation of STAT3 expression. Silencing of STAT3 also resulted in the inhibition of cell proliferation, migration and invasion of the AGS cells. Moreover, overexpression of STAT3 could nullify the tumor suppressive effects of miRNA-143 in AGS cells. Taken together, miRNA-143 has a tumor suppressive role in gastric cancer and may prove essential in gastric cancer treatment.