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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | 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 |
| Abstract | Background 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. Method 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. Results 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. Conclusion 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. |
| Related Links | https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-021-01314-w.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14764598 |
| DOI | 10.1186/s12943-021-01314-w |
| Journal | Molecular Cancer |
| Issue Number | 1 |
| Volume Number | 20 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2021-01-20 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology circSDHC E2F1 pathway miR-127-3p Renal cell carcinoma |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology Molecular Medicine Cancer Research |
| Journal Impact Factor | 27.7/2023 |
| 5-Year Journal Impact Factor | 31.3/2023 |
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