CircRNA PIP5K1A Promotes the Progression of Glioma Through Upregulation of the TCF12/PI3K/AKT Pathway by Sponging MiR-515-5p

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2021 Jan 8

PMID 33413401

Citations 31

Authors

Kebin Zheng

Haipeng Xie

Wensong Wu

Xichao Wen

Zhaomu Zeng

Yanfang Shi

Affiliations

Soon will be listed here.

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.

Citing Articles

Impact of UV-Irradiated Mesoporous Titania Nanoparticles (mTiNPs) on Key Onco- and Tumor Suppressor microRNAs of PC3 Prostate Cancer Cells.

Mendez-Garcia A, Bravo-Vazquez L, Sahare P, Paul S Genes (Basel). 2025; 16(2).

PMID: 40004477 PMC: 11855573. DOI: 10.3390/genes16020148.

Regulation of autophagy by non-coding RNAs in human glioblastoma.

Molavand M, Ebrahimnezhade N, Kiani A, Yousefi B, Nazari A, Majidinia M Med Oncol. 2024; 41(11):260.

PMID: 39375229 DOI: 10.1007/s12032-024-02513-3.

Emerging roles of CircRNA-miRNA networks in cancer development and therapeutic response.

Hashemi M, Khosroshahi E, Daneii P, Hassanpoor A, Eslami M, Koohpar Z Noncoding RNA Res. 2024; 10:98-115.

PMID: 39351450 PMC: 11440256. DOI: 10.1016/j.ncrna.2024.09.006.

The landscape of circRNAs in gliomas temozolomide resistance: Insights into molecular pathways.

Mafi A, Hedayati N, Kahkesh S, Khoshayand S, Alimohammadi M, Farahani N Noncoding RNA Res. 2024; 9(4):1178-1189.

PMID: 39022676 PMC: 11250881. DOI: 10.1016/j.ncrna.2024.05.010.

Osteosarcoma in a ceRNET perspective.

Mosca N, Alessio N, Di Paola A, Marrapodi M, Galderisi U, Russo A J Biomed Sci. 2024; 31(1):59.

PMID: 38835012 PMC: 11151680. DOI: 10.1186/s12929-024-01049-y.

References

Chi G, Xu D, Zhang B, Yang F . Matrine induces apoptosis and autophagy of glioma cell line U251 by regulation of circRNA-104075/BCL-9. Chem Biol Interact. 2019; 308:198-205. DOI: 10.1016/j.cbi.2019.05.030. View

Zhou R, Wu Y, Wang W, Su W, Liu Y, Wang Y . Circular RNAs (circRNAs) in cancer. Cancer Lett. 2018; 425:134-142. DOI: 10.1016/j.canlet.2018.03.035. View

Song H, Xu Y, Xu T, Fan R, Jiang T, Cao M . CircPIP5K1A activates KRT80 and PI3K/AKT pathway to promote gastric cancer development through sponging miR-671-5p. Biomed Pharmacother. 2020; 126:109941. DOI: 10.1016/j.biopha.2020.109941. View

Chi Y, Luo Q, Song Y, Yang F, Wang Y, Jin M . Circular RNA circPIP5K1A promotes non-small cell lung cancer proliferation and metastasis through miR-600/HIF-1α regulation. J Cell Biochem. 2019; 120(11):19019-19030. DOI: 10.1002/jcb.29225. View

Fang Y, Tan M, Zhou J, Liang L, Liu X, Zhao K . miR-214-3p inhibits epithelial-to-mesenchymal transition and metastasis of endometrial cancer cells by targeting TWIST1. Onco Targets Ther. 2019; 12:9449-9458. PMC: 6875683. DOI: 10.2147/OTT.S181037. View

Kristensen L, Hansen T, Veno M, Kjems J . Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2017; 37(5):555-565. PMC: 5799710. DOI: 10.1038/onc.2017.361. View

Gao S, Bian T, Zhang Y, Su M, Liu Y . TCF12 overexpression as a poor prognostic factor in ovarian cancer. Pathol Res Pract. 2019; 215(9):152527. DOI: 10.1016/j.prp.2019.152527. View

Sun Y, Li X, Chen A, Shi W, Wang L, Yi R . circPIP5K1A serves as a competitive endogenous RNA contributing to ovarian cancer progression via regulation of miR-661/IGFBP5 signaling. J Cell Biochem. 2019; 120(12):19406-19414. DOI: 10.1002/jcb.29055. View

Shu L, Zhang Z, Cai Y . MicroRNA-204 inhibits cell migration and invasion in human cervical cancer by regulating transcription factor 12. Oncol Lett. 2018; 15(1):161-166. PMC: 5768081. DOI: 10.3892/ol.2017.7343. View

10.

Qiao K, Ning S, Wan L, Wu H, Wang Q, Zhang X . LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway. J Exp Clin Cancer Res. 2019; 38(1):418. PMC: 6796384. DOI: 10.1186/s13046-019-1421-7. View

11.

Tong H, Zhao K, Wang J, Xu H, Xiao J . CircZNF609/miR-134-5p/BTG-2 axis regulates proliferation and migration of glioma cell. J Pharm Pharmacol. 2019; 72(1):68-75. DOI: 10.1111/jphp.13188. View

12.

Zhang X, Zhou J, Xue D, Li Z, Liu Y, Dong L . MiR-515-5p acts as a tumor suppressor via targeting TRIP13 in prostate cancer. Int J Biol Macromol. 2019; 129:227-232. DOI: 10.1016/j.ijbiomac.2019.01.127. View

13.

Pan Z, Lin J, Wu D, He X, Wang W, Hu X . Correction for: Hsa_circ_0006948 enhances cancer progression and epithelial-mesenchymal transition through the miR-490-3p/HMGA2 axis in esophageal squamous cell carcinoma. Aging (Albany NY). 2020; 12(4):4041-4044. PMC: 7066929. DOI: 10.18632/aging.102884. View

14.

Zhang Q, Zhang C, Ma J, Ren H, Sun Y, Xu J . Circular RNA PIP5K1A promotes colon cancer development through inhibiting miR-1273a. World J Gastroenterol. 2019; 25(35):5300-5309. PMC: 6761237. DOI: 10.3748/wjg.v25.i35.5300. View

15.

Reznik E, Smith A, Taube S, Mann J, Yondorf M, Parashar B . Radiation and Immunotherapy in High-grade Gliomas: Where Do We Stand?. Am J Clin Oncol. 2017; 41(2):197-212. DOI: 10.1097/COC.0000000000000406. View

16.

Abbasi A, Westerlaan H, Holtman G, Aden K, van Laar P, van der Hoorn A . Incidence of Tumour Progression and Pseudoprogression in High-Grade Gliomas: a Systematic Review and Meta-Analysis. Clin Neuroradiol. 2017; 28(3):401-411. PMC: 6105173. DOI: 10.1007/s00062-017-0584-x. View

17.

Cao Q, Shi Y, Wang X, Yang J, Mi Y, Zhai G . Circular METRN RNA hsa_circ_0037251 Promotes Glioma Progression by Sponging miR-1229-3p and Regulating mTOR Expression. Sci Rep. 2019; 9(1):19791. PMC: 6930248. DOI: 10.1038/s41598-019-56417-8. View

18.

Gao S, Bian T, Su M, Liu Y, Zhang Y . miR‑26a inhibits ovarian cancer cell proliferation, migration and invasion by targeting TCF12. Oncol Rep. 2019; 43(1):368-374. DOI: 10.3892/or.2019.7417. View

19.

Yan Y, Huang H . Interplay Among PI3K/AKT, PTEN/FOXO and AR Signaling in Prostate Cancer. Adv Exp Med Biol. 2020; 1210:319-331. DOI: 10.1007/978-3-030-32656-2_14. View

20.

Zheng S, Qi Y, Wu J, Zhou F, Yu H, Li L . CircPCMTD1 Acts as the Sponge of miR-224-5p to Promote Glioma Progression. Front Oncol. 2019; 9:398. PMC: 6538694. DOI: 10.3389/fonc.2019.00398. View