Downregulation of Decreases Survival Gene Expression, Promotes Apoptosis and Affects the Cell Cycle of Gastric Cancer Cells

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2022 Aug 18

PMID 35979166

Authors

Ana Flavia Teixeira Rossi

Fernanda da Silva Manoel-Caetano

Joice Matos Biselli

Agata Silva Cabral

Marilia de Freitas Calmon Saiki

Marcelo Lima Ribeiro

Ana Elizabete Silva

Affiliations

Soon will be listed here.

Abstract

Background: Chronic inflammation due to () infection promotes gastric carcinogenesis. Tumour necrosis factor-α (TNF-α), a key mediator of inflammation, induces cell survival or apoptosis by binding to two receptors (TNFR1 and TNFR2). TNFR1 can induce both survival and apoptosis, while TNFR2 results only in cell survival. The dysregulation of these processes may contribute to carcinogenesis.

Aim: To evaluate the effects of TNFR1 and TNFR2 downregulation in AGS cells treated with extract on the TNF-α pathway.

Methods: AGS cell lines containing TNFR1 and TNFR2 receptors downregulated by specific shRNAs and nonsilenced AGS cells were treated with extract for 6 h. Subsequently, quantitative polymerase chain reaction with TaqMan assays was used for the relative quantification of the mRNAs () and miRNAs (miR-19a, miR-34a, miR-103a, miR-130a, miR-181c) related to the TNF-α signalling pathway. Flow cytometry was employed for cell cycle analysis and apoptosis assays.

Results: In nonsilenced AGS cells, extract treatment increased the expression of genes involved in cell survival and inhibited both apoptosis ( and ) and the receptor. TNFR1 downregulation significantly decreased the expression of the and genes, although no change was observed in the cellular process or miRNA expression. In contrast, TNFR2 downregulation decreased the expression of the and genes, which are both important downstream mediators of the TNFR1-mediated pathway, as well as that of the and genes, while upregulating the expression of miR-19a and miR-34a Consequently, a reduction in the number of cells in the G0/G1 phase and an increase in the number of cells in the S phase were observed, as well as the promotion of early apoptosis.

Conclusion: Our findings mainly highlight the important role of TNFR2 in the TNF-α pathway in gastric cancer, indicating that silencing it can reduce the expression of survival and anti-apoptotic genes.

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