Biological function and mechanism of MALAT-1 in renal cell carcinoma proliferation and apoptosis: role of the MALAT-1–Livin protein interaction

• Published in: The journal of physiological sciences 2017-09, Vol.67 (5), p.577-585
• Main Authors: Chen, Shaoan, Ma, Pengpeng, Zhao, Ying, Li, Bin, Jiang, Shaobo, Xiong, Hui, Wang, Zheng, Wang, Hanbo, Jin, Xunbo, Liu, Chuan
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Animals; Apoptosis; Apoptosis - genetics; Carcinoma, Renal cell; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Cell Line; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Cell proliferation and metastasis; Cell Survival - genetics; Cholecystokinin; Development and progression; Female; Humans; Immunoprecipitation; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Livin; LncRNA MALAT-1; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lungs; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Original Paper; Polymerase chain reaction; Protein binding; Protein Interaction Maps - genetics; Proteins; Renal cell carcinoma; RNA; RNA, Long Noncoding - genetics; RNA-binding protein; Transcription; Tumor cell lines; Xenografts
• ISSN: 1880-6546; 1880-6562
• DOI: 10.1007/s12576-016-0486-8

Long noncoding RNAs (lncRNAs) have been shown to play a critical role in cancer development and progression. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) is a kidney cancer-associated onco-lncRNA involved in the progression of renal cell carcinoma (RCC). However, the pathological role of lncRNA MALAT-1 in RCC proliferation and metastasis remains poorly understood. This study was designed to investigate the biological role and mechanism of MALAT-1 in RCC proliferation and metastasis. The experiments were performed in human tissues, renal carcinoma cell lines, and nude mice. The expression of lncRNA MALAT-1, Livin mRNA, and the Livin protein was determined by quantitative real-time PCR (qRT-PCR) or a Western blot. The interaction between MALAT-1 and Livin was evaluated by RNA pull-down and RNA binding protein immunoprecipitation (RIP). Cell viability and apoptosis in RCC cell lines were detected using CCK-8 and TUNEL assays. LncRNA MALAT-1 and the Livin protein were highly expressed in RCC tissues, as well as in RCC 786-O and Caki-1 cell lines. MALAT-1 interference contributed to an increase in cell apoptosis and a reduction in the cell viability of 786-O and Caki-1 cells. The increase in apoptosis by si-MALAT-1 was reversed by overexpression of Livin. The RIP results showed that MALAT-1 promoted the expression of the Livin protein in 786-O and Caki-1 cells by enhancing the stability of the protein. Furthermore, the volume of si-MALAT-1-786-O cell xenograft was significantly suppressed. These data indicate that lncRNA MALAT-1-mediated promotion of RCC proliferation and metastasis may be due to the upregulation of the expression of Livin.