MiR193b Promotes Apoptosis of Gastric Cancer Cells via Directly Mediating the Akt Pathway.

Ruyue Tian,Shuilong Guo,Linlin Shao,Qingdong Guo,Bangwei Cao,Hailun Jiang,Yang Yu

doi:10.1155/2020/2863236

Abstract

Gastric cancer (GC) is one of the most common and fatal malignancies worldwide. MicroRNAs (miRNAs) play a critical role in tumor initiation, proliferation, and metastasis of gastric cancer. miR193b has been identified as a tumor suppressor in a variety of tumor types; however, its role in gastric cancer is yet to be determined. Here, we found a significant downregulation of miR193b expression in both human gastric cancer tissues (p < 0.05) and human gastric cancer cell lines (p < 0.01). Furthermore, the expression level of miR193b correlated with the tumor type, tumor size, and clinical stage (p < 0.05). In vitro, miR193b overexpression inhibited cell survival and induced apoptosis in GC cell lines, indicating that miR193b plays a role in the development of gastric cancer. KRAS was verified as the target of miR193b, and KRAS overexpression attenuated miR193b-induced apoptosis (p < 0.05). Moreover, we found that the Akt pathway negatively regulated miR193b, also affecting apoptosis. Further analyses indicated that PIK3CA mutation and KRAS amplification are two mutually exclusive pathways (p < 0.01), and we hypothesize that both two pathways could result in the carcinogenic overactivation of KRAS. Thus, our results suggest that the Akt-miR193b-KRAS axis may act as a mechanism affecting apoptosis in gastric cancer cells.

Highlights

Gastric cancer (GC) is the fifth most frequently occurring malignancy and ranks as the third leading cause of cancerrelated deaths worldwide [1]
The Expression of miR193b Is Downregulated in Human GC Tissue Samples, and miR193b Levels Are Correlated with Clinicopathological Features of Human Gastric Cancer
Using Quantitative Real-Time PCR, we found that miR193b expression was markedly lower in 5 different GC cell lines (AGS, N87, SNU-16, BGC-823, and SGC-7901) than in the normal epithelial cell line GES-1 (Figure 1(a), p < 0:01)

Summary

Introduction

Gastric cancer (GC) is the fifth most frequently occurring malignancy and ranks as the third leading cause of cancerrelated deaths worldwide [1]. There has been considerable progress in uncovering the genetic alterations driving tumor initiation and growth in this condition, the molecular mechanisms underlying GC progression require further investigation [2]. Exploring this issue will help in identifying novel diagnostic and therapeutic targets for human gastric cancer. MiRNAs have been shown to target several apoptosis-related genes, such as Mcl-1 (miR512-5p), bcl-2 (miR34), MIF (miR451), and EGR2 (miR150). MiRNA deregulation can promote cell cycle progression, migration, and invasion, by altering the levels or translation of their target mRNA [9]

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Conclusion