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Neoplasma Vol.67, No.6, p.1293–1302, 2020 |
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Title: miR-877-5p antagonizes the promoting effect of SP on the gastric cancer progression | ||
Author: Xiao-Dan Guo, Nan Zhang, Lei Sha | ||
Abstract: Gastric cancer is one of the four major tumors in the world and the second leading cause of cancer-related death. It was reported that Substance P (SP), as an oncogenic factor, could regulate the expression of miRNAs in gastric cancer progression. Here, we focused on the role of miR-877-5p in gastric cancer development and the miR-877-5p involvement in the SP-mediated gastric cancer development. The mRNA expression level and cell proliferation were assessed by quantitative real-time PCR and cell counting kit-8 assay, respectively. Flow cytometry was conducted to detect apoptosis, followed by assessing the expression of related apoptosis factors. Dual-luciferase reporter assay was performed to validate the interaction between miR-877-5p and Forkhead cassette M1 (FOXM1). Our results showed that SP treatment significantly increased cell proliferation in gastric cancer. Moreover, the miR-877-5p expression was dose-dependently decreased by SP, whereas FOXM1 expression was markedly increased by SP in gastric cancer cells. miR-877-5p negatively regulated gastric cancer development via inhibiting cell proliferation and promoting apoptosis accompanied by increased cleaved caspase-3, cleaved caspase-9, and bax protein levels and decreased bcl-2 level. We confirmed that miR-877-5p could target FOXM1 and negatively regulate its expression. Furthermore, we demonstrated that SP could promote cell proliferation and inhibit apoptosis, while miR-877-5p overexpression reversed the effect of SP on cell proliferation and apoptosis. These results suggest that miR-877-5p overexpression can antagonize the promoting effect of SP on the development of gastric cancer, indicating that miR-877-5p may serve as a promising therapeutic target for gastric cancer. |
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Keywords: gastric cancer; Substance P; miR-877-5p; cell proliferation; apoptosis | ||
Published online: 27-Aug-2020 | ||
Year: 2020, Volume: 67, Issue: 6 | Page From: 1293, Page To: 1302 | |
doi:10.4149/neo_2020_200502N480 |
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