Circular RNA_0000629 Suppresses Bladder Cancer Progression Mediating MicroRNA-1290/CDC73

Abstract

Background

Recent studies showed circular RNAs (circRNAs) played regulatory roles in bladder cancer (BC). However, the relevance of circ_0000629, a newly identified circRNA, has not been determined yet. We aimed to characterize the function of circ_0000629 in BC and the relevant mechanism.

Methods

First, we downloaded circRNA-related microarrays GSE147985 and GSE92675 from the GEO database, followed by a validation in our clinically obtained samples. We then overexpressed circ_0000629 in T24 and SW780 cells and evaluated the effects of circ_0000629 on BC cell proliferatory, apoptotic, and metastatic abilities. We further detected the subcellular localization of circ_0000629 in T24 and SW780 cells by the fractionation and export assay and FISH experiments. Integrated microarray analyses and bioinformatics website prediction were utilized to screen out the downstream microRNA (miRNA)/mRNA. The effects of miR-1290 and CDC73 on BC cell growth and metastasis was verified by functional rescue experiments. In addition, mice xenografts were built to measure the effect of circ_0000629 on tumor growth in vivo.

Results

Circ_0000629 and CDC73 were reduced, and miR-1290 was significantly overexpressed in BC tissues and cells. Moreover, circ_0000629 significantly inhibited the development and metastasis of BC cells, but further overexpression of miR-1290 or knockdown of CDC73 attenuated the inhibitory effect of circ_0000629 on BC cells. Circ_0000629 localized in the cytoplasm and regulated CDC73 expression by sponging miR-1290. Further, overexpressed circ_0000629 reduced the BC tumor growth in vivo.

Conclusion

Circ_0000629 promotes the expression of CDC73 by competitively binding to miR-1290, thereby inhibiting the growth and metastasis of BC cells.

Keywords:

• bladder cancer
• circular RNA_0000629
• microRNA-1290
• CDC73
• epigenetics

Data Sharing Statement

All the data generated or analyzed during this study are included in this published article.

Ethics Approval and Consent to Participate

This study was approved by the Research and Ethical Committee of Hunan Provincial People’s Hospital and conducted in accordance with the Declaration of Helsinki. Participants signed informed consents prior to sample collection. Experimental procedures were approved by the Institutional Committee on the Care and Use of Animals of Hunan Provincial People’s Hospital. All animals received humane care according to the National Institutes of Health (USA) guidelines.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no potential conflicts of interest.