Circular RNA CEP128 promotes bladder cancer progression by regulating Mir‐145‐5p/Myd88 via MAPK signaling pathway

• Published in: International journal of cancer 2019-10, Vol.145 (8), p.2170-2181
• Main Authors: Sun, Ming, Zhao, Wenyan, Chen, Zhaofu, Li, Ming, Li, Shuqiang, Wu, Bin, Bu, Renge
• Format: Article
• Language: English
• Subjects: Apoptosis; Assaying; Bladder cancer; Cancer; Cell cycle; Cell Line; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell Proliferation - genetics; Cell viability; circCEP128; Circular RNA; Computer programs; Disease Progression; DNA microarrays; Flow cytometry; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Gene Ontology; Gene Regulatory Networks; Humans; Immunoprecipitation; Kinases; MAP kinase; MAP Kinase Signaling System - genetics; MAPK signaling pathway; Medical research; MicroRNAs - genetics; Microtubule Proteins - genetics; miR‐145‐5p; MYD88; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Proteins; RNA, Circular - genetics; Signal transduction; Tissues; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Viability; Wound healing; Xenografts
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32311

The present experiment was designed for exploring the regulatory mechanism of circ‐CEP128/miR‐145‐5p/MYD88 axis in bladder cancer. MiRNAs and circRNAs expression data were derived from Gene Expression Omnibus database with bladder tumor tissues and paracarcinoma tissue samples. Differentially expressed genes in tumor were analyzed via R software. Interaction network of differently expressed miRNAs and differently expressed mRNA was established by means of Cytoscape software. CircCEP128 and miR‐145‐5p expression levels were determined using qRT‐PCR. The expression of MAPK signaling‐related proteins MYD88, p38, ERK and JNK was examined by western blot. The relationship between circCEP128 and miR‐145‐5p was validated using RNA immunoprecipitation. The level of cell propagation and migration was determined by CCK8 and wound healing assay, 5‐bromo‐2′‐deoxyuridine assay and migration assay. Cell apoptosis rate and cell cycle were detected via flow cytometry. Tumor xenograft assay was implemented to investigate the function of circCEP128 in vivo. CircCEP128 and MYD88 were overexpressed in bladder cancer based on microarray analysis and miR‐145‐5p was a potential targeting factor in bladder cancer. CircCEP128 targeted miR‐145‐5p and miR‐145‐5p targeted MYD88. Expression of miR‐145‐5p was decreased in cancer samples. Knockdown of circCEP128 induced the inhibition of cell viability and mobility and cell cycle arrest. Overexpression of miR‐145‐5p or knockdown of circCEP128 promoted MAKP signaling pathway and related proteins expression. In addition, knockdown of circCEP128 suppressed the growth of bladder cancer tumor tissues in vivo. Overexpression of circCEP128 promoted bladder cancer progression through modulating miR‐145‐5p and MYD88 via MAKP signaling pathway. What's new? Noncoding circular RNAs (circRNAs), which feature covalently linked ends and are highly stable RNAs, were once considered functionless. These molecules, however, are now known to serve diverse cellular roles and likely influence cancer development. In this study, the circRNA CEP128, frequently overexpressed in bladder cancer, was investigated in the context of tumor progression. CircCEP128 expression increased with advancing bladder tumor stage. Its upregulation was accompanied by microRNA‐145‐5p downregulation and upregulation of MYD88 and MAPK signaling proteins. The data suggest that the circCEP128/miR‐145‐5p/MYD88 axis influences bladder cancer progression and is a potential source of novel