Hsa_circ_0001944 promotes the growth and metastasis in bladder cancer cells by acting as a competitive endogenous RNA for miR-548

• Published in: Journal of experimental & clinical cancer research 2020-09, Vol.39 (1), p.186-186
• Main Authors: Jin, Mingming, Lu, Shengjie, Wu, Yue, Yang, Chen, Shi, Chunzi, Wang, Yanqiu, Huang, Gang
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Animals; Apoptosis; Binding sites; Biomarkers; Biomarkers, Tumor - genetics; Bladder cancer; Cancer metastasis; Cell cycle; Cell growth; Cell Proliferation; Cholecystokinin; Development and progression; Experiments; Female; Fluorescence; Gene expression; Gene Expression Regulation, Neoplastic; Health savings accounts; hsa_circ_0001944; Humans; Luciferase; Lymphatic Metastasis; Male; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; miR-548; Neoplasm Invasiveness; Prognosis; PROK2; Proliferation; RNA; RNA, Circular - genetics; Stains & staining; Survival Rate; Tumor Cells, Cultured; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Wound healing; Xenograft Model Antitumor Assays
• ISSN: 0392-9078; 1756-9966; 1756-9966
• DOI: 10.1186/s13046-020-01697-6

Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.