Circular RNA circ_001842 plays an oncogenic role in renal cell carcinoma by disrupting microRNA‐502‐5p‐mediated inhibition of SLC39A14

Abstract

Renal cell carcinoma (RCC) is a common urologic malignancy, and up to 30% of RCC patients present with locally advanced or metastatic disease at the time of initial diagnosis. Increasing evidence suggests that circular RNAs (circRNAs) serve as genomic regulatory molecules in various human cancers. Our initial in silico microarray‐based analysis identified that circRNA circ_001842 was highly expressed in RCC. Such up‐regulation of circ_001842 in RCC was experimentally validated in tissues and cell lines using RT‐qPCR. Thereafter, we attempted to identify the role of circ_001842 in the pathogenesis of RCC. Through a series of gain‐ and loss‐of function assays, cell biological functions were examined using colony formation assay, Transwell assay, annexin V‐FITC/PI‐labelled flow cytometry and scratch test. A high expression of circ_001842 in tissues was observed as associated with poor prognosis of RCC patients. circ_001842 was found to elevate SLC39A14 expression by binding to miR‐502‐5p, consequently resulting in augmented RCC cell proliferation, migration and invasion, as well as EMT in vitro and tumour growth in vivo. These observations imply the involvement of circ_001842 in RCC pathogenesis through a miR‐502‐5p‐dependent SLC39A14 mechanism, suggesting circ_001842 is a potential target for RCC treatment.

CircNT5E promotes the proliferation and migration of bladder cancer via sponging miR-502-5p

“…In gastric cancer, miR-502-5p inhibited the growth and metastasis of gastric cancer cells in vitro and in vivo by blocking the NRAS/MEK1/ERK1/2 signal pathway 28 . In renal cell carcinoma (RCC), miR-502-5p impaired the proliferation and metastasis of RCC cells via decreasing SLC39A14 expression 29 . In Bca, miR-502-5p restrained cell proliferation and migration in vitro and in vivo via interacting with CCND1, NOP14 and DNMT3B 30 .…”

Systematic Review With Meta-Analysis: Diagnostic, Prognostic and Clinicopathological Significance of CircRNA Expression in Renal Cancer

“…Of the 207 studies, we also excluded studies unrelated to RC or circRNAs, irrelevant records, reviews and other studies that did not meet the requirements of format and content, leaving 77 studies. After the analysis and evaluation of the remaining 77 studies, we found that some studies did not meet the inclusion criteria, and a total of 22 studies were actually available for reference after elimination (15,16,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). Among them, 18 were related to prognosis, 4 were related to diagnosis, and 12 were related to clinicopathology.…”

Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

“…Circ_0001368 was also identified as a novel anti-tumor RNA via negatively regulating the miR-492/LATS2 axis ( 57 ). Several other circRNA-miRNA-mRNA interaction cascades have been reported in RCC, most of which were found with tumor promotive effects, including circ_001895/miR-296-5p/SOX12 ( 53 ), circ_001842/miR-502-5p/SLC39A14 ( 54 ), circ-EGLN3/miR-1299/IRF7 ( 56 ), circ_0039569/miR-34a-5p/CCL22 ( 83 ), circ-ZNF609/miR-138-5p/FOXP4 ( 84 ), and circ_0054537/miR-130a-3p/cMet ( 85 ). Intriguingly, several circRNAs have been reported to work as miRNA reservoirs to regulate RCC development ( 86 , 87 ).…”