Circular RNA SERPINE2 promotes development of glioblastoma by regulating the miR-361-3p/miR-324-5p/BCL2 signaling pathway

Abstract

Circular RNA (circRNA) is a new type of long-sequence RNA formed by a noncanonical form of alternative splicing called back-splicing. Emerging evidence has revealed that circRNAs are involved in cancer progression, regulating cancer-related genes through sponging microRNAs (miRNAs). In our study, we identified a novel upregulated circRNA, circSERPINE2 , through analyzing circRNAs microarray data of glioblastoma from GEO datasets (GSE146463). Quantitative real-time PCR was used to further confirm the upregulation of circSERPINE2 in glioblastoma cell lines and tissues. Silencing circSERPINE2 inhibits glioblastoma proliferation in vivo and in vitro through cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry analysis, and western blot analysis and xenograft tumor model. Mechanistically, circSERPINE2 could directly sponge miR-324-5p and miR-361-3p. BCL2 , known as a novel anti-apoptosis gene, is a target gene both of miR-324-5p and miR-361-3p. Thus, circSERPINE2 promotes BCL2 expression through sponging miR-324-5p and miR-361-3p. In conclusion, our study revealed the biological function and mechanism of circSERPINE2 in glioblastoma progression and that circSERPINE2 could be a potential therapeutic target for glioblastoma.

[Retracted] The Function of circRNA‐0047604 in Regulating the Tumor Suppressor Gene DACH1 in Breast Cancer

“…Recent reports indicate that circRNA can act as miRNA sponge and interacting with proteins to affect gene expression level to influence transcription and translation [ 37 – 39 ]. After further analyzing circRNA on breast cancer sample, we found that circ_0047604 expression level is lower in tumors.…”

A review on the role of miRNA-324 in various diseases

“…Different experiments in brain tumors have confirmed tumor suppressor role of miR-324. For instance, SERPINE2 has been found to induce proliferation of glioblastoma cells and inhibit their apoptosis via influencing activity of miR-324-5p/BCL2 axis ( Li et al, 2021 ). Moreover, the oncogenic lncRNA NEAT1 promotes progression of glioma through sponging miR-324-5p and inducing expression of KCTD20 ( Zhang et al, 2021 ).…”

Research Progress of circRNAs in Glioblastoma

“…Found that circ-FOXO3 can bind both miR-138-5p and miR-432-5p to regulate NFAT5 expression and thus promote cell proliferation ( Zhang S. et al, 2019 ). Li et al, Found that the circ-SERPINE2-miR-361-3p/miR-324-5p/BCL2 signaling pathway plays an important role in the tumor growth process of GBM ( Li D. et al, 2021 ). Besides, hsa_circ_0008344 ( Zhou et al, 2018 ), hsa_circ_0029426 ( Zhang G. et al, 2019 ), hsa_circ_0067934 ( Xin et al, 2019 ), circ-SKA3 ( Zhou M. et al, 2021 ), circ-PARP4 ( Zhou J. et al, 2021 ), circ-FLN1 ( Sun et al, 2021 ) and circ-NF1( Liu L. et al, 2021 ) were also shown to significantly promote the proliferative capacity and tumor growth of GBM cells, but the specific molecular mechanisms remain to be further explored.…”

“…To further analyze the prognostic value of circRNAs in GBM, we evaluated the association of circRNAs expression levels with the overall survival (OS) rate of GBM patients. Twelve upregulated circRNAs were reported to predict poorer OS in GBM patients ( Zhang G. et al, 2019 ; Qian et al, 2019 ; Xin et al, 2019 ; Zhu et al, 2020 ; Chen B. et al, 2021 ; Li D. et al, 2021 ; Liu L. et al, 2021 ; Wang Q. et al, 2021 ; Wu X. et al, 2021 ; Zhou M. et al, 2021 ; Sun et al, 2021 ), and three downregulated circRNAs predicted poorer OS in GBM patients ( Zhang X. et al, 2019 ; Lv et al, 2020 ; Wang T. et al, 2021 ). It was shown that lower expression of has_circ_0067934 was associated with longer disease-free survival (DFS) ( Xin et al, 2019 ).…”