Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis

Abstract

Background Circular RNAs (circRNAs) have been considered to mediate occurrence and development of human cancers, generally acting as microRNA (miRNA) sponges to regulate downstream genes expression. However, the aberrant expression profile and dysfunction of circRNAs in human bladder cancer remain to be investigated. The present study aims to elucidate the potential role and molecular mechanism of circACVR2A in regulating the proliferation and metastasis of bladder cancer. Methods circACVR2A (hsa_circ_0001073) was identified by RNA-sequencing and validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The role of circACVR2A in bladder cancer was assessed both in vitro and in vivo. Biotin-coupled probe pull down assay, biotin-coupled microRNA capture, dual-luciferase reporter assay, and fluorescence in situ hybridization were conducted to evaluate the interaction between circACVR2A and microRNAs. Results The expression of circACVR2A was lower in bladder cancer tissues and cell lines. The down-regulation of circACVR2A was positively correlated with aggressive clinicopathological characteristics, and circACVR2A served as an independent risk factor for overall survival in bladder cancer patients after cystectomy. Our in vivo and in vitro data indicated that circACVR2A suppressed the proliferation, migration and invasion of bladder cancer cells. Mechanistically, we found that circACVR2A could directly interact with miR-626 and act as a miRNA sponge to regulate EYA4 expression. Conclusions circACVR2A functions as a tumor suppressor to inhibit bladder cancer cell proliferation and metastasis through miR-626/EYA4 axis, suggesting that circACVR2A is a potential prognostic biomarker and therapeutic target for bladder cancer. Electronic supplementary material The online version of this article (10.1186/s12943-019-1025-z) contains supplementary material, which is available to authorized users.

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

“…These characteristics indicate that circRNAs have distinct properties and diverse cellular regulatory functions, including the regulation of cellular processes, such as proliferation and apoptosis (21)(22)(23). Furthermore, it has been revealed that circRNAs have crucial regulatory functions in various aspects of cancer, such as tumorigenesis (24), proliferation, migration, invasion (25), metastasis (26), apoptosis, and chemotherapy and radiation resistance (27,28), as well as in cancer prognosis (29).…”

“…Function of exosomal circRNAs. Several studies have reported that circRNAs can function in cancer by either promoting or inhibiting tumour progression and regulating the biological behaviour of malignant tumours, including cell proliferation, migration, invasion and metastasis (26,85,86). However, circRNAs in exosomes are still rarely studied.…”

CircPVT1 Promotes Bladder Cancer Progression by Acting as a ceRNA for miR-140-3p to Target TRPS1

“…Studies have reported that circular RNA is involved in the pathogenesis of BC. [16][17][18] In our research, we found that circPVT1 expression was higher in BC tissues and cell lines and was signi cantly increased in metastatic tissues compared with non-metastatic tissues.…”

A Multi-Omics Analysis of Bone Morphogenetic Protein 5 (BMP5) mRNA Expression and Clinical Prognostic Outcomes in Different Cancers Using Bioinformatics Approaches

“…BAMBI is also reported to be overexpressed in breast and ovarian cancer and co-translocate with Smads into the nucleus upon TGF-β treatment [79,80]. Circular ACVR2A expression was found to be suppressed in bladder cancer tissues and cell lines and has a functional role in bladder cancer inhibition and metastasis [81]. CHRD was found to be significantly under-expressed in ovarian cancer compared to normal tissues suggesting its potential of regulating BMP activity in normal ovarian surface epithelium physiology [82].…”