Abstract
BackgroundIncreasing 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.MethodsFirstly, 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.ResultsThe 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.ConclusionsOverall, 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.
Highlights
Increasing studies have revealed that circular RNAs (CircRNAs) make great contributions to regulating tumor progression
By detecting the expression of circPIP5K1A, miR-515-5p, Transcription factor 12 (TCF12) and PI3K/AKT in glioma tissues and cells and exploring the relationship among these molecules, we discovered that circPIP5K1A inhibits the miR-515-5p level and upregulates TCF12 by serving as a competitive endogenous RNA of miR-515-5p, which in turn affects glioma cell proliferation and metastasis
The circPIP5K1A expression in different glioma cell lines was compared by reverse transcription-polymerase chain reaction (RT-PCR), and the results manifested that it was obviously upregulated in glioma cell lines (U87, TJ861, TJ905, U251, H4, and A172) compared with that in normal human glial cells (HEB) (P < 0.05, Fig. 1b)
Summary
Increasing studies have revealed that circular RNAs (CircRNAs) make great contributions to regulating tumor progression. We intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A, in glioma. Circ-0006948 directly binds to miR-490-3p, which targets the 3′UTR of the oncogene high mobility group protein A2 (HMGA2) in esophageal squamous cell carcinoma (ESCC). Circ-0006948 enhances HMGA2 expression by sponging miR-490-3p, inducing EMT and aggravating ESCC [6]. Circ-0037251 affects glioma cell proliferation and metastasis by regulating the miR-1229-3p/mTOR axis [7]. CircPIP5K1A is a newly discovered cancer-related circRNA, which is a powerful regulator in tumors. Zhang Qu et al demonstrated that overexpressing circPIP5K1A enhances AP-1 expression and dampens the expression of IRF-4, CDX-2, and Zic-1 by downregulating miR-1273a, facilitating the migration and invasion of colon cancer [8]. The mechanism of action of circPIP5K1A in other diseases, including glioma, is rarely reported
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