Circular RNA UBAP2 contributes to tumor growth and metastasis of cervical cancer via modulating miR-361-3p/SOX4 axis

Abstract

Background Increasing researches have reported that circular RNA UBAP2 (circUBAP2) may be a potential prognosis biomarker and participate in the development of several cancers; however, the role of circUBAP2 in cervical cancer (CC) remains largely unclear. Methods We applied qRT-PCR and Western blot to examine expression levels of circUBAP2, miR-361-3p, SOX4, Bax, Bcl-2, Cleaved caspase 3, N-cadherin, Vimentin and E-cadherin. Cell proliferation, apoptosis, invasion and migration were analyzed by MTT assay, Flow cytometry, and Transwell assay, respectively. The interaction between miR-361-3p and circUBAP2 or SOX4 was confirmed by luciferase reporter assay and pull-down assay. Murine xenograft model was established by injecting SiHa cells which stably transfected sh-circUBAP2. Results CircUBAP2 was up-regulated in CC tissues and cell lines and high circUBAP2 expression predicated poor outcome. Knockdown of circUBAP2 suppressed cell proliferation, migration, invasion and EMT, while induced apoptosis in CC in vitro, and inhibited tumor growth and metastasis in vivo. MiR-361-3p directly bound to circUBAP2 or SOX4, and circUBAP2 could regulate SOX4 expression by sponging miR-361-3p in CC cells. Furthermore, rescue assay results demonstrated that the inhibitory effects of circUBAP2 knockdown on cell growth and metastasis were partially reversed by miR-361-3p down-regulation or SOX4 up-regulation in CC. Conclusion CircUBAP2 represents a prognostic marker and contributes to tumor growth and metastasis via modulating miR-361-3p/SOX4 axis in CC, which indicates a potential therapeutic target for CC treatment.

Circular RNA Circ_0003221 Promotes Cervical Cancer Progression by Regulating miR-758-3p/CPEB4 Axis

“… 7 , 8 Currently, many reports have suggested that circRNAs can serve as oncogenes or tumor suppressors in multiple cancers, including cervical cancer. 9 , 10 Recently, circRNAs are one of the new targets for cervical cancer, such as circUBAP2, 11 hsa_circ_0000069, 12 circ_0005576, 13 circSLC26A4 14 have been identified to promote cervical cancer progression, suggesting the important role of circRNAs in cervical cancer tumorigenesis. As for circ_0003221 (also known as circPTK2, chr8:141856358–141900868), it has been demonstrated to be overexpressed in cervical cancer cells.…”

Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis

“…circUBAP2 modulates pancreatic adenocarcinoma tumorigenesis by regulating the levels of hsa-miR-494 and the expression of CXCR4, HIF1A, ZEB1, SDC1, and TWIST1 32 . In addition, circUBAP2 modulates cancer cell malignancy through the miR-641/YAP1 axis and miR-361-3p/SOX4 axis in osteosarcoma and cervical cancer, respectively 33 , 34 . Consistently, our results showed that circUBAP2 silencing was sufficient to attenuate HCC cell migration, as well as the promotive effects of CXCL11 on HCC cell migration.…”

The Role of the SOX9/lncRNA ANXA2P2/miR-361-3p/SOX9 Regulatory Loop in Cervical Cancer Cell Growth and Resistance to Cisplatin

“…Reportedly, miR-361-3p plays a tumor-suppressive role in multiple cancers, including non-small cancer lung cancer ( 13 , 36 – 38 ), prostate cancer ( 39 ), thyroid cancer ( 16 ), and cervical cancer ( 15 , 40 , 41 ). Although previous studies have indicated the aberrant downregulation of miR-361-3p in regular cervical cancer cell lines and cervical cancer tissues ( 15 , 40 , 41 ), this study demonstrated the significant downregulation of miR-361-3p in DDP-resistant cervical cancer cells and tissues for the first time. Consistent with the expression trend, miR-361-3p overexpression remarkably inhibited the growth of DDP-resistant cervical cancer cells.…”