CircWHSC1 expedites cervical cancer progression via miR-532-3p/LTBP2 axis.

Abstract

Dysregulated circRNAs have potential roles in the progression of various cancer types, including cervical cancer (CaCx). The carcinogenic roles of circRNA Wolf-Hirschhorn syndrome candidate gene-1 (circWHSC1) are described in the development of diverse cancers. The objective of this study was to investigate the expression and the underlying role of circWHSC1 in CaCx. The expression of circWHSC1 was detected by real-time PCR. After the suppression of circWHSC1 expression, the changes in the proliferation, migration, invasion, and apoptosis capacities were detected by CCK-8 assay, colony formation assay, Transwell assays, flow cytometry, and the determination of apoptosis-related proteins. The interplay among circWHSC1, miR-532-3p, and latent transforming growth factor-β binding protein 2 (LTBP2) was confirmed by luciferase reporter and biotinylated RNA pull-down assays. A nude mice xenograft tumor model was established to evaluate the anti-tumorigenic role of circWHSC1 silencing in vivo. CircWHSC1 was overexpressed in CaCx tissues and cell lines and its high expression was inversely associated with the survival rate of patients with CaCx. CircWHSC1 silencing was capable of suppressing the proliferation, metastasis, and invasion of tumor cells and inducing apoptosis. Investigation to its molecular mechanism revealed that circWHSC1 functioned as a competitive endogenous RNA (ceRNA), mediating LTBP2 expression by targeting miR-532-3p. The in vivo experiments further confirmed the inhibition of tumor growth and metastasis by circWHSC1 knockdown. The circWHSC1-mediated miR-532-3p/LTBP2 signaling axis might be a novel therapeutic target for CaCx.

• Authors: Yan Li, Fandong Meng, Chengguang Sui, Yang Wang, Dali Cheng
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 477 Issue 6 Pg. 1669-1679 (Jun 2022) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 35235125 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• LTBP2 protein, human
• Latent TGF-beta Binding Proteins
• MIRN532 microRNA, human
• MicroRNAs
• RNA, Circular

Topics

• Animals
• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Latent TGF-beta Binding Proteins (genetics, metabolism)
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• RNA, Circular (genetics)
• Uterine Cervical Neoplasms (genetics)