miR193b Promotes Apoptosis of Gastric Cancer Cells via Directly Mediating the Akt Pathway

Abstract EN

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.