title: Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205.
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.
authors.affiliation: Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
authors.affiliation: Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California.
authors.forename: Varahram
authors.initials: V
authors.lastname: Shahryari
authors.affiliation: Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California.
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.affiliation: Department of Urology, Toho University Faculty of Medicine, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Pathology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California.
authors.forename: Z Laura
authors.initials: ZL
authors.lastname: Tabatabai
authors.affiliation: Department of Urology, Toho University Faculty of Medicine, Tokyo, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California. rdahiya@urology.ucsf.edu.
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D000071221:Enhancer of Zeste Homolog 2 Protein; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2; D016760:Proto-Oncogene Proteins c-fos; D062085:RNA, Long Noncoding; C557041:MALAT1 long non-coding RNA, human; C534425:MIR205, human; C498409:EZH2 protein, human