Regulator of G-protein signalling 3 and its regulator microRNA-133a mediate cell proliferation in gastric cancer

Abstract

Background and study aims: Regulator of G-protein signalling 3 (RGS3) plays a pivotal role in Wnt signalling and epithelial-mesenchymal transition. RGS3 overexpression in gastric cancer suggests that RGS3 and its regulators have the potential to serve as therapeutic targets for gastric cancer. Therefore, we aimed to investigate the roles of RGS3 and its regulator microRNA-133a in gastric cancer tumorigenesis.

Material and methods: mRNA and protein expression levels of RGS3 in 107 paired human gastric cancer tissues and gastric cancer cells were examined using qRT-PCR and immunoblotting, respectively. The relationship between RGS3/microRNA-133a expression and clinicopathological characteristics was assessed using t-test. TargetScan, miRanda and MicroCosm Targets were employed to predict the binding site on the 3'-untranslated region of RGS3 that is targeted by microRNA-133a. Moreover, dual-luciferase reporter assay was performed to validate target prediction. microRNA-133a expression level in gastric cancer tissues and cell lines was determined by qRT-PCR. Finally, the proliferation activity of gastric cancer cells was evaluated using Cell Counting Kit-8 and bromodeoxyuridine incorporation assays.

Results: RGS3 expression level markedly increased in both gastric cancer tissues and cells compared with that in the corresponding normal tissues and cells. However, microRNA-133a expression level markedly decreased in gastric cancer tissues and cells and was negatively correlated with RGS3 expression. Higher RGS3 and lower microRNA-133a expression levels were associated with a larger tumour size, lymph node metastasis, local invasion and advanced tumour-node-metastasis stage in gastric cancer. Dual-luciferase reporter assay verified that microRNA-133a targeted RGS3 via mRNA 3'-untranslated region binding. Finally, microRNA-133a inhibited gastric cancer cell proliferation, whereas RGS3 overexpression attenuated this inhibitory effect.

Conclusion: MicroRNA-133a is a regulator of RGS3 in gastric cancer and the microRNA-133a-RGS3 axis possibly participates in the malignant progression of gastric cancer.

Keywords: Cell proliferation; Gastric cancer; MicroRNA; Regulator of G-protein signalling 3.