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. 2021 Dec;12(2):11376-11389.
doi: 10.1080/21655979.2021.2008659.

Circular RNA circFLNA inhibits the development of bladder carcinoma through microRNA miR-216a-3p/BTG2 axis

Shuangquan Lin  1 , Lei Wang  2 , Zimin Shi  1 , Anyi Zhu  1 , Gan Zhang  1 , Zhengdong Hong  1 , Cheng Cheng  1
Affiliations

Circular RNA circFLNA inhibits the development of bladder carcinoma through microRNA miR-216a-3p/BTG2 axis

Shuangquan Lin et al. Bioengineered. 2021 Dec.

Abstract

Recent studies have shown that circular RNA circFLNA is abnormally expressed in a variety of malignant tumors, but its role and mechanism in bladder carcinoma (BCa) are still unclear. The present paper aims to contribute to research on the effects and mechanism of circFLNA on the malignant phenotype of BCa. In this study, the expressions of circFLNA, miR-216a-3p and BTG2 in BCa and BCa cells (EJ, T24, 5637, TCC-SUP) were detected by qRT-PCR. EdU staining, colony formation, Transwell assay, wound healing assays, and sphere formation assay were used to measure the cell proliferation, viability, invasion, migration, and cell stemness of BCa cells after circFLNA overexpression. In addition, the correlation existed between miR-216a-3p and circFLNA or BTG2 was confirmed by Dual-Luciferase Reporter assay and RNA pull-down. Western blot was utilized to determine the expression of BTG2, MMP2, epithelial-mesenchymal transition (EMT)-related proteins (vimentin, E-cadherin) and stem cell-specific proteins (CD34, OCT4, SOX2). Our study confirmed that downregulated circFLNA and BTG2 expression and upregulated miR-216a-3p were found in both BCa tissues and cell lines. Meanwhile, upregulated circFLNA inhibited proliferation, invasion and migration, EMT and stemness of BCa cells. MiR-216a-3p was a target gene of circFLNA and could target BTG2. Further analysis finally demonstrated that circFLNA sponged miR-216a-3p and indirectly promoted BTG2 expression, ultimately regulating proliferation, migration, invasion and EMT of BCa cells. In conclusion, circFLNA inhibits the malignant phenotype of BCa cells and their stemness through miR-216a-3p/BTG2, thus suppressing BCa progression.

Keywords: BTG2; CircFLNA; bladder carcinoma; malignant phenotype; miR-216a-3p; stem cells.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Downregulation of circFLNA expression in bladder carcinoma tissues and cells
Figure 2.
Figure 2.
Effect of circFLNA on the proliferation, invasion, and migration of bladder carcinoma cells
Figure 3.
Figure 3.
Effect of circFLNA on bladder carcinoma cell stemness
Figure 4.
Figure 4.
Association between circFLNA and miR-216a-3p expression
Figure 5.
Figure 5.
MiR-216a-3p affects inhibitory effect of circFLNA on cell viability and proliferation (a) qRT-PCR-based detection of miR-216a-3p expression in 5637 cells, **P < 0.01 vs. NC mimics group, ##P < 0.01 vs. NC inhibitor group; (b, c) 5637 cell viability was detected by colony formation assay (b), and proliferation by EdU assay (c), **P < 0.01 vs. Vector + NC mimics group, ##P < 0.01 vs. circFLNA + NC mimics group
Figure 6.
Figure 6.
MiR-216a-3p affects inhibitory effect of circFLNA on cell invasion and migration
Figure 7.
Figure 7.
Effect of miR-216a-3p on circFLNA-caused inhibition of the stemness of bladder carcinoma cells
Figure 8.
Figure 8.
Association among circFLNA, miR-216a-3p, and BTG2
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Science and Technology Plan of Jiangxi Provincial Health Commission (No. 20201064).