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Cancer Res. 2015 Apr 1;75(7):1322-31. doi: 10.1158/0008-5472.CAN-14-2931. Epub 2015 Jan 19.

Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205.

Author information

1
Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California.
2
Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
3
Department of Urology, Toho University Faculty of Medicine, Tokyo, Japan.
4
Department of Pathology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California.
5
Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California. rdahiya@urology.ucsf.edu.

Abstract

Recently, long noncoding RNAs (lncRNA) have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). In this study, we investigated the contributions of the lncRNA MALAT1 in RCC with a specific focus on its transcriptional regulation and its interactions with Ezh2 and miR-205. We found that MALAT1 expression was higher in human RCC tissues, where it was associated with reduced patient survival. MALAT1 silencing decreased RCC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas β-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. Lastly, MALAT1 bound Ezh2 and oncogenesis facilitated by MALAT1 was inhibited by Ezh2 depletion, thereby blocking epithelial-mesenchymal transition via E-cadherin recovery and β-catenin downregulation. Overall, our findings illuminate how overexpression of MALAT1 confers an oncogenic function in RCC that may offer a novel theranostic marker in this disease.

PMID:
25600645
PMCID:
PMC5884967
DOI:
10.1158/0008-5472.CAN-14-2931
[Indexed for MEDLINE]
Free PMC Article

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