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miR-200c Targets CDK2 and Suppresses Tumorigenesis in Renal Cell Carcinoma
Xuegang Wang1, 5, Xuanyu Chen1, Weiwei Han1, Anming Ruan1, Li Chen1, Rong Wang1, Zhenghong Xu2, Pei Xiao2, Xing Lu2, Yan Zhao2, Jia Zhou2, Shaoyong Chen3, Quansheng Du4, Hongmei Yang2* and Xiaoping Zhang1*
1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022; 2Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China; 3Cancer Biology Program, Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA; 4Department of Neurology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; 5Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China.
Running Title: miR-200c inhibits cell proliferation in renal cell carcinoma. Key words: microRNA-200c; CDK2; renal cell carcinoma; cell cycle Corresponding Authors: To Xiaoping Zhang, Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China. Phone: 86-27-85351625; Email: [email protected].
To Hongmei Yang, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei Province, China. Phone: 86-27-83691053; Email: [email protected].
Grant support:
This research was supported by National Natural Science Foundation of China (Grant No. 30872924, 81072095 & 81372760), Program for New Century Excellent Talents in University from Department of Education of China (NCET-08-0223) and the National High Technology Research and Development Program of China (863 Program) (2012AA021101) to X.Z, and supported by National Natural Science Foundation of China (Grant No. 31070142 & 81272560) to H.Y.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Other notes
Our manuscript contains 4,566 words and seven figures and three tables.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
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Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Table 2. The correlation between miR-200c and ccRCC with TNM stage, Fuhrman classification and tumor size.
*p: Tumor diameter≤3cm group vs. diameter 3-5cm group. **p: Tumor diameter 3-5cm group vs. diameter≥5cm group. ***p: Tumor diameter≤3cm group vs. diameter≥5cm group. ****p: Tumor diameter<5cm group vs. diameter≥5cm group.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Table 3. Incidence of renal tumor and tumor weight in orthotopic xenografts after 6 and 7 weeks.
Tumor incidence (%) Tumor weight (mg)
mean±SEM Group NO. of mice 6th week 7th week 6th week 7th week miR-Ctr 12 6/6 (100%) 6/6 (100%) 84.10 ± 8.509 86.22 ± 11.35 miR-200c 12 6/6 (100%) 6/6 (100%) 28.17 ± 2.762 38.22 ± 3.864 p value NS NS 0.0274 0.0437 1. p values were determined by Fisher exact test. 2. Tumor weights were calculated: weight of left kidney – weight of right kidney. If the tumor xenograft weight was small and the left kidney was just slightly heavier than the right, the weight of the tumor was recorded as zero. 3. NS:Not significant.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 6, 2015; DOI: 10.1158/1541-7786.MCR-15-0128
Published OnlineFirst August 6, 2015.Mol Cancer Res Xuegang Wang, Xuanyu Chen, Weiwei Han, et al. Renal Cell CarcinomamiR-200c Targets CDK2 and Suppresses Tumorigenesis in
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