CircRNA PIP5K1A promotes the progression of glioma through upregulation of the TCF12/PI3K/AKT pathway by sponging miR-515-5p

Abstract

Background Increasing studies have revealed that circular RNAs (CircRNAs) make great contributions to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A, in glioma. Methods Firstly, reverse transcription-polymerase chain reaction (RT-PCR) was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical-pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and CircPIP5K1A overexpression and knockdown cell models were constructed. Subsequently, cell proliferation and viability were detected by the CCK8 method and BrdU staining. Cell apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (Caspase3, Bax, and Bcl2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin, and N-cadherin) was determined by western blot or RT-PCR. Results The results manifested that CircPIP5K1A was upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated glioma cell proliferation, invasion, and EMT and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A upregulated TCF12 and PI3K/AKT activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3′-untranslated region (UTR) of TCF12. Conclusions Overall, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates glioma evolvement by modulating the miR-515-5p-mediated TCF12/PI3K/AKT axis.

Circular RNA: A novel type of biomarker for glioma (Review)

“…Thus, the identification of valuable biomarkers for early-stage diagnosis and prognosis is crucial for improving the survival of patients with glioma. Recent studies have demonstrated that circRNAs are strongly associated with the clinicopathological characteristics of glioma, and they may serve as diagnostic and prognostic biomarkers ( 32 , 92 , 110 ). Previous studies indicated that the closed-ring structure stabilizes circRNAs in plasma and tissues, and protects them from the enzymatic activity of exonucleases ( 28 , 50 ); therefore, the unique structure of circRNAs may be a potential advantage for their use as biomarkers for the diagnosis and prognosis of glioma.…”

Research Progress on Circular RNA in Glioma

“…Circ-MAPK4 and circ-POSTN were also associated with improved tumor size and WHO grade. Additionally, circPIP5K1A ectopic expression may also be associated with glioma volume and histopathological grade ( 82 ).…”

“…In addition to FBXW7-185aa described earlier, circ-MAPK4 sponges miR-125a-3p to inhibit glioma cell apoptosis via downregulating P38/MAPK phosphorylation levels ( 44 ). Activation of P38/MAPK is correlated with the apoptosis of nerve cells and tumor cells ( 82 , 83 ).…”

“…The natural product matrine can induce apoptosis and autophagy in glioma cells by downregulating the PI3K/AKT and Wnt-β-catenin pathways ( 145 ). CircPIP5K1A and circNT5E can modulate PI3K/AKT downstream signaling via sponging miR-515-5p and miR-422a, respectively, thereby promoting glioma proliferation and metastasis ( 82 , 84 ). Furthermore, circPCMTD1 and hsa_circ_0037251 promote glioma cell proliferation and metastasis by regulating the mammalian target of rapamycin (mTOR) pathway via sponging of miR-224-5p and miR-1229-3p, respectively ( 146 ).…”

Circular RNA circPIP5K1A contributes to cancer stemness of osteosarcoma by miR-515-5p/YAP axis

“…It is now widely accepted that circRNAs usually act as sponges for microRNAs (miRNAs) to participate in various cellular behaviors, including cell proliferation, differentiation, apoptosis and migration, etc., and are even recognized as oncogenes or tumour suppressors [ 6 ]. Among the functional circular RNAs, circPIP5K1A is proposed to facilitate the progression of several cancers, including gastric cancer [ 7 ], ovarian cancer [ 8 ], non-small cell lung cancer (NSCLC) [ 9 ], colon cancer [ 10 ], and glioma [ 11 ]. However, the function of circPIP5K1A in osteosarcoma is not yet identified.…”