Circular RNA FAM114A2 suppresses progression of bladder cancer via regulating ∆NP63 by sponging miR-762.

Abstract

Numerous evidences have shown that circular RNAs (circRNAs) play a key role in regulating the pathogenesis of cancer. However, the mechanism of circRNAs in urothelial carcinoma of bladder (UCB) remains largely unclear. In this study, we found circFAM114A2 was significantly downregulated both in UCB tissue specimens and cell lines, and the expression level was highly correlated with pathological TNM stage and grade. Functionally, overexpression of circFAM114A2 dramatically inhibited the migration, invasion and proliferation of UCB cells in vitro, and suppressed tumor growth in vivo. Mechanistically, we confirmed miR-762 was copiously pulled down by circFAM114A2 in 5637 and T24 cells. Fluorescence in situ hybridization (FISH) further indicated the cytoplasmic interactions between circFAM114A2 and miR-762. By using luciferase reporter assay, we found that miR-762 could directly target TP63. Subsequently, we found that circFAM114A2 might increase the expression of ∆NP63 (main isoform of TP63 in UCB) by sponging miR-762. Taken together, our results demonstrated that circFAM114A2 might serve as a competing endogenous RNA (ceRNA) of miR-762 in regulating the expression of ∆NP63, thus suppressed UCB progression through circFAM114A2/miR-762/∆NP63 axis.

• Authors: Tianyao Liu, Qun Lu, Jin Liu, Shangxun Xie, Baofu Feng, Wenjie Zhu, Minghui Liu, Yanqing Liu, Xinyan Zhou, Wu Sun, Yujing Zhang, Xi Chen, Feng Fang, Hongqian Guo, Rong Yang
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 1 Pg. 47 (01 22 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 31969560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• MIRN762 microRNA, human
• MicroRNAs
• RNA, Circular
• TP63 protein, human
• Transcription Factors
• Tumor Suppressor Proteins

Topics

• 3' Untranslated Regions (genetics)
• Aged
• Animals
• Base Sequence
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease Progression
• Down-Regulation (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Muscles (pathology)
• Neoplasm Invasiveness
• RNA, Circular (genetics, metabolism)
• Transcription Factors (metabolism)
• Tumor Suppressor Proteins (metabolism)
• Urinary Bladder Neoplasms (genetics, pathology)