Expression of miR-141 and YAP1 in gastric carcinoma and modulation of cancer cell proliferation and apoptosis

Int J Clin Exp Pathol. 2019 Feb 1;12(2):559-567. eCollection 2019.


Yes-associated protein 1 (YAP1) plays important roles in facilitating cell proliferation and decreasing apoptosis and is related to gastric cancer. Abnormal down-regulation of miR-141 is associated with gastric cancer pathogenesis, suggesting a potentially tumor suppressor role. Bioinformatics analysis found complementary binding sites between miR-141 and YP1. This study investigated the role of miR-141 in mediating YAP1 expression and biological behavior of gastric cancer cells. Gastric cancer tissues were collected using normal mucosal tissues as the control. qRT-PCR compared expression of miR-141 and YAP1 mRNA, and western blot quantified YAP1 protein expression. Spearman approach analyzed the correlation between miR-141 and YAP1 mRNA in cancer tissues. Dual luciferase reporter gene assay confirmed the targeted regulation between miR-141 and YAP1. Using GES-1 cell as the control, miR-141 and YAP1 expression were measured in gastric cancer cell lines SGC7901 and MGC03. Those cells were transfected with miR-141 mimic in the presence or absence of miR-YAP1 mimic followed by flow cytometry for apoptosis and EdU staining for proliferation. Cancer tissues had decreased miR-141 and higher YAP1 expression, which was associated with TNM stage. YAP1 mRNA and miR-141 were positively correlated (r=-0.623, P<0.001). Dual luciferase assay demonstrated targeted regulation between miR-141 and YAP1. Comparing to GES-1 cells, SGC7901 and MGC803 cells had decreased miR-141 and increased YAP1 expression. Transfection of miR-141 mimic inhibited YAP1 expression or cell proliferation and facilitated apoptosis. However, overexpression of YAP1 decreased the effect of miR-141 mimic on cell proliferation and apoptosis. miR-141 down-regulation and YAP1 up-regulation are correlated with gastric cancer pathogenesis. miR-141 targets and inhibits YAP1 expression, to suppress gastric cancer cell proliferation and induce apoptosis.

Keywords: Gastric cancer; YAP1; apoptosis; cell proliferation; miR-141.