Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

• Published in: Molecular cancer Vol. 20; no. 1; pp. 19 - 14
• Main Authors: Cen, Junjie, Liang, Yanping, Huang, Yong, Pan, Yihui, Shu, Guannan, Zheng, Zhousan, Liao, Xiaozhong, Zhou, Mi, Chen, Danlei, Fang, Yong, Chen, Wei, Luo, Junhang, Zhang, Jiaxing
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.01.2021; BioMed Central; BMC
• Subjects: Analysis; Animals; Antibodies; Base Sequence; Binding sites; Bioinformatics; Biomarkers; Carcinogenesis - genetics; Carcinogenesis - pathology; Carcinoma, Renal cell; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Cell adhesion & migration; Cell culture; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; Chromosome 3; circSDHC; Circular RNA; Cyclin-Dependent Kinase Inhibitor Proteins - metabolism; Cytogenetics; Development and progression; Disease Progression; DNA microarrays; Down-Regulation - genetics; Dual-Specificity Phosphatases - metabolism; E2F1 pathway; E2F1 Transcription Factor - metabolism; Female; Fluorescence in situ hybridization; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Male; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-127-3p; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Metastasis; Patients; Plasmids; Prognosis; Proportional Hazards Models; Proteins; Renal cell carcinoma; Ribonucleic acid; RNA; RNA, Circular - genetics; RNA, Circular - metabolism; Signal Transduction; Therapeutic targets; Tumors; United States > US; China; Germany; E2F1 pathway; miR-127-3p; Renal cell carcinoma; circSDHC
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-021-01314-w

There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.