LncRNA LOC653786 promotes growth of RCC cells via upregulating FOXM1.

Fan Yang,Haojun Xiong,Bo Li,Min Xu,Xinzhe Li,Qingjian Wu,Fengtian He,Kebin Zhang,Yan Zhang,Le Zhang,Wei Xie

doi:10.18632/oncotarget.24027

Abstract

Renal cell carcinoma (RCC) is the most common kidney malignancy with poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been demonstrated as important regulators in multiple cancers including RCC. LOC653786 is a lncRNA, but its role in cancer remains unclear. In this study, we for the first time found that LOC653786 was upregulated in RCC tissues and cell lines, and this lncRNA promoted growth and cell cycle progression of RCC cells. Moreover, we showed that LOC653786 elevated the expression of forkhead box M1 (FOXM1) and its downstream target genes cyclin D1 and cyclin B1 in RCC cells. Reporter assay revealed that LOC653786 enhanced the transcriptional activity of FOXM1 gene promoter. Additionally, knockdown of FOXM1 attenuated the LOC653786-enhanced growth and cell cycle progression of RCC cells. Meanwhile, silencing of LOC653786 suppressed RCC cell growth and cell cycle progression, which was alleviated by overexpression of FOXM1. The in vivo experiments in nude mice showed knockdown of LOC653786 repressed xenograft tumor growth and FOXM1 expression. In conclusion, our results demonstrate that LOC653786 accelerates growth and cell cycle progression of RCC cells via upregulating FOXM1, suggesting that the ‘LOC653786/FOXM1’ pathway may serve as a novel target for RCC treatment.

Highlights

Renal cell carcinoma (RCC) is the most common malignancy of kidney which accounts for approximate 2%3% of human malignant neoplasms [1], and its incidence and mortality are rising these years [2]
The above results demonstrate that RCC tissues and cell lines have a higher level of LOC653786, suggesting that LOC653786 may play an important role in RCC development and progression, and this long noncoding RNAs (lncRNAs) may serve as a novel potential biomarker and therapeutic target of RCC
Previous reports have shown that the mutations on Von HippelLindau (VHL), Polybromo-1 (PBRM1) and BRCA1 associated protein-1 (BAP1) are the most common somatic mutations in Clear cell renal carcinoma (ccRCC) which induces the occurrence and development of ccRCC [25]

Summary

Introduction

Renal cell carcinoma (RCC) is the most common malignancy of kidney which accounts for approximate 2%3% of human malignant neoplasms [1], and its incidence and mortality are rising these years [2]. Clear cell renal carcinoma (ccRCC) represents the most common RCC, which occupies about 75%-80% of RCC [1]. Some lncRNAs (such as MALAT1, HOTAIR, LncARSR, etc.) have shown importance in RCC [17,18,19,20,21,22]. It remains largely unknown about the profiles of lncRNAs in RCC

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Results

Conclusion