DNA-methylation-mediated repression of miR-766-3p promotes cell proliferation via targeting SF2 expression in renal cell carcinoma
Chen Chen
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Search for more papers by this authorSheng Xue
Department of Urology, Shanghai Tenth People's Hospital, Nanjing Medical University, Nanjing, China
Department of Urology, The First Affliated Hospital of Bengbu Medical College Bengbu, Anhui, China
Search for more papers by this authorJin Zhang
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Search for more papers by this authorWei Chen
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Search for more papers by this authorDongkui Gong
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Search for more papers by this authorJiayi Zheng
Department of Pathology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Search for more papers by this authorJunjie Ma
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Search for more papers by this authorWei Xue
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Search for more papers by this authorCorresponding Author
Yonghui Chen
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Correspondence to: Yonghui Chen, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Wei Zhai, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Junhua Zheng, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072, China, E-mail: [email protected]; Fax: +86 02166307508Search for more papers by this authorCorresponding Author
Wei Zhai
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Correspondence to: Yonghui Chen, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Wei Zhai, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Junhua Zheng, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072, China, E-mail: [email protected]; Fax: +86 02166307508Search for more papers by this authorCorresponding Author
Junhua Zheng
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Correspondence to: Yonghui Chen, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Wei Zhai, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Junhua Zheng, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072, China, E-mail: [email protected]; Fax: +86 02166307508Search for more papers by this authorChen Chen
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Search for more papers by this authorSheng Xue
Department of Urology, Shanghai Tenth People's Hospital, Nanjing Medical University, Nanjing, China
Department of Urology, The First Affliated Hospital of Bengbu Medical College Bengbu, Anhui, China
Search for more papers by this authorJin Zhang
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Search for more papers by this authorWei Chen
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Search for more papers by this authorDongkui Gong
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Search for more papers by this authorJiayi Zheng
Department of Pathology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Search for more papers by this authorJunjie Ma
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Search for more papers by this authorWei Xue
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Search for more papers by this authorCorresponding Author
Yonghui Chen
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Correspondence to: Yonghui Chen, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Wei Zhai, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Junhua Zheng, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072, China, E-mail: [email protected]; Fax: +86 02166307508Search for more papers by this authorCorresponding Author
Wei Zhai
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127 China
Correspondence to: Yonghui Chen, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Wei Zhai, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Junhua Zheng, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072, China, E-mail: [email protected]; Fax: +86 02166307508Search for more papers by this authorCorresponding Author
Junhua Zheng
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072 China
Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Correspondence to: Yonghui Chen, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Wei Zhai, Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China, E-mail: [email protected]; Junhua Zheng, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072, China, E-mail: [email protected]; Fax: +86 02166307508Search for more papers by this authorConflict of Interest: The authors declare that they have no conflict of interest.
Abstract
Aberrant expression of microRNA (miRNA) emerges as an important role in a wide range of human malignances, and further identification as well as validation of the change of these endogenous non-protein-coding transcripts is warranted. Here, we identify a novel epigenetic regulation of miR-766-3p and investigate its biological function as well as clinical significance in renal cell carcinoma (RCC). Bisulfate analysis elucidates that the promoter of miR-766-3p is highly methylated in RCC tissues compared to non-tumorous tissues. Notably, the downregulation of miR-766-3p is obviously associated with clinical stage and worse prognosis in RCC patients. Upregulated miR-766-3p attenuates cell-cycle progression via targeting SF2 expression and additional SF2/P-AKT/P-ERK signaling pathway. Moreover, high level of SF2, as a novel oncoprotein in RCC, was significantly associated with poor survival in a large cohort of RCC specimens. Taken together, our study presents a road map for the prediction and validation of miR-766-3p/SF2 axis and thus imparts a therapeutic way for further RCC progression.
Abstract
What's new?
Changes in the expression of microRNAs (miRNAs) are now known for a variety of cancers, though their significance remains unclear. In our study, miR-766-3p, a suspected inducer or inhibitor of tumor growth in different cancers, was investigated in renal cell carcinoma (RCC). MiR-766-3p was found to be downregulated and highly methylated in RCC patient tissues. Its downregulation, the result of promoter suppression by DNA methylation, was associated with reduced overall survival. In RCC cells, miR-766-3p upregulation attenuated cell-cycle progression and suppressed cell proliferation. The findings indicate that MiR-766-3p, as an antitumor miRNA, is of therapeutic relevance in RCC.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| ijc30853-sup-0001-suppfig1.tif18.6 MB | FIGURE 1: miR-766-3p inhibits renal cancer cell-cycle progression in vitro and in vivo |
| ijc30853-sup-0002-suppfig2.tif8 MB | FIGURE 2: miR-766-3p is regulated by DNA methylation |
| ijc30853-sup-0003-suppfig3.tif17.8 MB | FIGURE 3: miR-766-3p directly targets SF2 |
| ijc30853-sup-0004-suppfig4.tif19.7 MB | FIGURE 4: shRNA-SF2 attenuated cell proliferation |
| ijc30853-sup-0005-supptable1.xlsx13.6 KB | Table S1. Clinical characteristics of 75 RCC patients according to miRNA-766-3p expression levels |
| ijc30853-sup-0006-supptable2.xlsx10.8 KB | Table S2. Univariate and Multivariate Cox Regression Analyses of miR-766-3p Expression Levels and Overall Cancer Survival in Subjects with RCC |
| ijc30853-sup-0007-supptable3.xlsx13.6 KB | Table S3. Clinical characteristics of 238 RCC patients according to SF2 expression levels |
| ijc30853-sup-0008-supptable4.xlsx12.5 KB | Table 4: ANOVA analysis of the value of different SF2 group |
| ijc30853-sup-0009-supptable5.xlsx10.8 KB | Table S5. Univariate and Multivariate Cox Regression Analyses of SF2 Expression Levels and Overall Cancer Survival in Subjects With RCC. |
| ijc30853-sup-0010-supptable6.xlsx10 KB | Table S6. Primers used for reverse transcription and real-time PCR |
| ijc30853-sup-0011-supptable7.xlsx9.7 KB | Table S7. Primers used for vectors construction |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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