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Liu F, Wu L, Wang A, et al. MicroRNA-138 attenuates epithelial-to-mesenchymal transition by targeting SOX4 in clear cell renal cell carcinoma. Am J Transl Res. 2017;9(8):3611-3622
Liu, F., Wu, L., Wang, A., Xu, Y., Luo, X., Liu, X., Hua, Y., Zhang, D., Wu, S., Lin, T., He, D., Wei, G., & Chen, S. (2017). MicroRNA-138 attenuates epithelial-to-mesenchymal transition by targeting SOX4 in clear cell renal cell carcinoma. American journal of translational research, 9(8), 3611-3622.
Liu, Feng, et al. "MicroRNA-138 attenuates epithelial-to-mesenchymal transition by targeting SOX4 in clear cell renal cell carcinoma." American journal of translational research vol. 9,8 (2017): 3611-3622.
Liu F, Wu L, Wang A, Xu Y, Luo X, Liu X, Hua Y, Zhang D, Wu S, Lin T, He D, Wei G, Chen S. MicroRNA-138 attenuates epithelial-to-mesenchymal transition by targeting SOX4 in clear cell renal cell carcinoma. Am J Transl Res. 2017 Aug 15;9(8):3611-3622. eCollection 2017. PMID: 28861152; PMCID: PMC5575175.
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Am J Transl Res. 2017 Aug 15;9(8):3611-3622. eCollection 2017.

MicroRNA-138 attenuates epithelial-to-mesenchymal transition by targeting SOX4 in clear cell renal cell carcinoma.

American journal of translational research

Feng Liu, Linfeng Wu, Anping Wang, Yajun Xu, Xiaodong Luo, Xing Liu, Yi Hua, Deying Zhang, Shengde Wu, Tao Lin, Dawei He, Guanghui Wei, Shanwen Chen

Affiliations

  1. Department of Urinary Surgery, Children's Hospital, Chongqing Medical UniversityChongqing, China.
  2. Wenzhou Hospital of Integrated Traditional Chinese and Western MedicineWenzhou, Zhejiang, China.
  3. Department of Neurology, Xiangyang No.1 People's Hospital, Hubei University of MedicineXiangyang, Hubei, China.
  4. Daqing Oil Field General HospitalDaqing, Heilongjiang, China.
  5. Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical UniversityChongqing, China.
  6. Department of Urology, Huashan Hospital Affiliated to Fudan UniversityShanghai, China.

PMID: 28861152 PMCID: PMC5575175

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs which can serve as oncogenes or tumor suppressor genes in human cancers. Herein, the transcriptomic differences of miRNAs in ccRCC were globally assessed using publicly available microarray dataset (GSE71302) from Gene Expression Omnibus (GEO) and we identified miR-138 as a potential onco-suppressive miRNA. We further found that the expression of miR-138 was dramatically decreased in ccRCC cell lines and clinical ccRCC tissue samples, and the low miR-138 expression was closely correlated with tumor progression and prognosis in ccRCC patients. Overexpression of miR-138 inhibited, whereas downregulation of miR-138 promoted, the proliferation, migration and invasion of ccRCC cells in vitro, suggesting that miR-138 may function as a tumor suppressor in ccRCC. Furthermore, for the first time, we identified the EMT-related transcription factor SOX4 as a direct target gene of miR-138, evidenced by the direct binding of miR-138 with the 3'UTR of SOX4. Notably, the EMT marker E-cadherin or vimentin was also upregulated or downregulated upon miR-138 overexpression, and these effects were restored by SOX4 overexpression. We have also shown SOX4 overexpression reversed the attenuated migratory and invasive capacities mediated by miR-138. These results revealed that miR-138 functions as a tumor suppressor in ccRCC by targeting SOX4 and the EMT process and might represent a potential target in the treatment of human ccRCC.

Keywords: Clear cell renal cell carcinoma; SOX4; epithelial-mesenchymal transition; miR-138; tumorigenicity

Conflict of interest statement

None.

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