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 realtime 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.

The circular RNA circ_GRHPR promotes NSCLC cell proliferation and invasion via interactions with the RNA‐binding protein PCBP2

“…FHL3 interacts with transcription factors and multiple cell‐signalling molecules in glioma, breast cancer, and liver cancer 9,10,23 . Although most studies mentioned that FHL3 is a tumour suppressor, we identified that FHL3 promotes NSCLC cell proliferation and invasion, potentially affecting the biological behaviour of NSCLC cells by disturbing the cell cycle via P27 and invasion by the TGF‐β signalling pathway, as reported in other studies 10,11 . Meanwhile, the tumour‐promoting effect of FHL3 is closely correlated with the survival rate and prognosis.…”

“…According to reports by Niu 10 and Mao, 11 genes such as P27, TGF‐β, and Smad2/3 are the downstream targets of FHL3. We examined expression of these genes in NSCLC cells and found that FHL3 overexpression inhibited P27 expression, disturbing the cell cycle and promoting the expression of TGF‐β and Smad2/3—all of which promote cell invasion (Figure 5D ).…”

“… 9 , 10 , 23 Although most studies mentioned that FHL3 is a tumour suppressor, we identified that FHL3 promotes NSCLC cell proliferation and invasion, potentially affecting the biological behaviour of NSCLC cells by disturbing the cell cycle via P27 and invasion by the TGF‐β signalling pathway, as reported in other studies. 10 , 11 Meanwhile, the tumour‐promoting effect of FHL3 is closely correlated with the survival rate and prognosis. Taken together, these results demonstrate that FHL3 acts as a tumour‐promoting factor in NSCLC.…”

RNA m1A Methyltransferase TRMT6 Predicts Poorer Prognosis and Promotes Malignant Behavior in Glioma

“…However, the TGF-beta pathway is significantly activated in malignant gliomas, and the activation of TGF-beta pathway was closely associated with malignant progression and poor prognosis ( Roy et al, 2015 ). The experimental study demonstrated that PCBP2 could activate TGF-beta pathway, thus promoting the development and progression of glioma ( Mao et al, 2020 ). In summary, the aforementioned results showed that TRMT6 may be involved in glioma progression by regulating cell cycle, PI3K-AKT, TGF-beta, MTORC1, NOTCH, and MYC pathways.…”

Transforming Growth Factor-Beta-Regulated LncRNA-MUF Promotes Invasion by Modulating the miR-34a Snail1 Axis in Glioblastoma Multiforme

“…TGF-b is overexpressed in glioblastoma, and its elevated expression is associated with the increased histologic grade of GBM (6). TGF-b promotes proliferation, invasion, metastasis, angiogenesis, resistance to apoptosis, replicative immortality, evasion of growth suppression, evasion of immune checkpoint blockade, and chemoresistance in GBM (7)(8)(9).…”