Rgs4 regulates proliferation and apoptosis of nsclc cells via microrna-16 and brain-derived neurotrophic factor

Abstract

Purpose: Regulator of G-protein signaling (RGS) proteins are GTPase-activating proteins that target the α-subunit of heterotrimeric G proteins. Many studies have shown that RGS proteins contribute to tumorigenesis and metastasis. However, the mechanism in which RGS proteins, especially RGS4, affect the development of non-small cell lung cancer (NSCLC) remains unclear. The aim of this study was to characterize the role of RGS4 in NSCLC. Methods: RGS4 expression in NSCLC tissues was assessed using an immunohistochemistry tissue microarray. Additionally, RGS4 was knocked down using short-hairpin RNA to assess the regulatory function of RGS4 in the biological behaviors of human NSCLC cell lines. A xenograft lung cancer model in nude BALB/c mice was established to study whether RGS4 knockdown inhibits cancer cell proliferation in vivo. Results: We observed an increase in RGS4 protein levels in NSCLC samples. RGS4 knockdown inhibited cell proliferation and induced apoptosis in H1299 and PC9 cell lines, but did not affect cell migration. Moreover, we found that RGS4 negatively regulated the expression of microRNA-16 (miR-16), a tumor suppressor. The inhibition of miR-16 resulted in upregulated RGS4 expression. We also found that RGS4 regulated the expression of brain-derived neurotrophic factor (BDNF) and activated the BDNF-tropomyosin receptor kinase B signaling pathway. Conclusion: This study revealed that RGS4 overexpression positively correlated with the development of NSCLC. TDownstream RGS4 targets (eg, miR-16 and BDNF) might be involved in the development of NSCLC and may serve as potential therapeutic targets for its treatment.