PCBP2 promotes the development of glioma by regulating FHL3/TGF-β/Smad signaling pathway.

Abstract

The purpose of this study was to investigate the role of Poly (C)‐binding protein 2 (PCBP2) and the related signaling pathway in glioma progression. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and immunohistochemistry (IHC) were performed to measure PCBP2 messenger RNA and protein expression in glioma tissues or cells. Cell transfection was completed using Lipofectamine 2000. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, Transwell assay and flow cytometry assay were used to explore the effects of PCBP2 expression on biological behaviors of glioma cells. Western blot assay was used for the detection of pathway related proteins. Expression of PCBP2 in glioma tissues and cells were higher than that in paracancerous tissues and normal cells (both p < .01). Moreover, the elevated expression of PCBP2 was significantly correlated with tumor size (p = .001) and WHO stage (p = .010). Knockdown of PCBP2 could suppress proliferation, migration and invasion of glioma cells and promote apoptosis. Besides, the expression of transforming growth factor‐β (TGF‐β) pathway related proteins TGF‐β1, p‐Smad2 and p‐Smad7 were decreased following the downregulation of PCBP2. PCBP2 also inhibited FHL3 expression by binding to FHL3‐3′UTR. The inhibition of FHL3 could reverse the antitumor action caused by PCBP2 silencing. In vivo assay, PCBP2 was also found to inhibit the tumor growth of glioma. PCBP2 activates TGF‐β/Smad signaling pathway by inhibiting FHL3 expression, thus promoting the development and progression of glioma.