circCHST15 is a novel prognostic biomarker that promotes clear cell renal cell carcinoma cell proliferation and metastasis through the miR-125a-5p/EIF4EBP1 axis

• DOI: 10.1186/s12943-021-01449-w
• Publication Date: 2021-12-18T09:02:39Z
• Authors: Cheng-Peng Gui; Bing Liao; Cheng-Gong Luo; Yu-Hang Chen; Lei Tan; Yi-Ming Tang; Jia-Ying Li; Yi Hou; Hong-De Song; Hai-Shan Lin; Quan-Hui Xu; Gao-Sheng Yao; Hao-Hua Yao; Xi-Liu; Jun-Hang Luo; Jia-Zheng Cao; Jin-Huan Wei
• Keywords: Clear cell renal cell carcinoma; Adult; Male; Proliferation; Cell Cycle Proteins; miR-125a-5p; Models, Biological; Metastasis; Mice; 03 medical and health sciences; Cell Line, Tumor; Biomarkers, Tumor; Animals; Humans; Carcinoma, Renal Cell; RC254-282; Adaptor Proteins, Signal Transducing; Aged; EIF4EBP1; 0303 health sciences; Membrane Glycoproteins; Research; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Middle Aged; Kidney Neoplasms; 3. Good health; Gene Expression Regulation, Neoplastic; Disease Models, Animal; MicroRNAs; hsa_circ_0020303; Heterografts; Female

Abstract Background Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting microRNA (miRNA) sponges to regulate downstream gene expression. However, the aberrant expression profile and dysfunction circRNAs human clear cell renal carcinoma (ccRCC) need be further investigated. This study mined key prognostic elucidates potential role molecular mechanism regulating proliferation metastasis ccRCC. Methods circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from Gene Expression Omnibus database comparing matched versus adjacent normal epithelial tissue pairs or primary metastatic pairs. These results were validated quantitative real-time polymerase chain reaction agarose gel electrophoresis. We demonstrated biological effect ccRCC both vitro vivo. To test interaction between miRNAs, we conducted a number experiments, including RNA pull down assay, dual-luciferase reporter assay fluorescence situ hybridization. Results The higher tissues compared healthy kidney RCC lines lines. level positively correlated with aggressive clinicopathological characteristics, served an independent indicator for overall survival progression-free patients after surgical resection. Our vivo data indicate that promotes proliferation, migration, invasion cells. Mechanistically, found directly interacts miR-125a-5p acts sponge EIF4EBP1 Conclusions sponging promote is underlying hsa_circ_0020303-induced progression. prompts investigation biomarker therapeutic target