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Cell Death Differ. 2017 Sep;24(9):1502-1517. doi: 10.1038/cdd.2017.74. Epub 2017 Jun 23.

LncRNA-SARCC suppresses renal cell carcinoma (RCC) progression via altering the androgen receptor(AR)/miRNA-143-3p signals.

Zhai W1,2,3, Sun Y3, Guo C1,3, Hu G1, Wang M3,4, Zheng J5, Lin W3, Huang Q3, Li G4, Zheng J1, Chang C3,6.

Author information

1
Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
2
Department of Urology, Renji Hospital, School of Medicine in Shanghai Jiao Tong University, 160 Pujian Road, Pudong District, Shanghai 200127, China.
3
George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14646 USA.
4
Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
5
Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
6
Sex Hormone Research Center, China Medical University/Hospital, Taichung 404, Taiwan.

Abstract

While the androgen receptor (AR) might promote renal cell carcinoma (RCC) initiation and progression, the molecular mechanisms involved remain largely unclear. Here, we discovered the novel LncRNA-SARCC, which was suppressed and associated with better prognosis in RCC. Preclinical studies using multiple RCC cells and in vivo mouse model indicated that LncRNA-SARCC could attenuate RCC cell invasion, migration and proliferation in vitro and in vivo. Mechanistically, LncRNA-SARCC bound and destabilized AR protein with an inhibition of AR function, which led to transcriptionally de-repress miR-143-3p expression, thus inhibition of its downstream signals including AKT, MMP-13, K-RAS and P-ERK. In addition, bisulfite sequencing analysis substantiated that LncRNA-SARCC promoter was highly methylated in renal cancer tissues compared with paired non-cancerous renal tissues. Notably, treating with Sunitinib, the multi-targeted receptor tyrosine kinase inhibitor, increased the expression of LncRNA-SARCC, which decreased RCC cells resistance to Sunitinib. Thus, our study presented a road map for targeting this newly identified LncRNA-SARCC and its pathway, which expands potential therapeutic strategies for RCC treatment.

PMID:
28644440
PMCID:
PMC5563985
DOI:
10.1038/cdd.2017.74
[Indexed for MEDLINE]
Free PMC Article

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