Long noncoding RNA PVT1 inhibits renal cancer cell apoptosis by up-regulating Mcl-1.

Qingjian Wu,Zhenxing Yang,Wanlei Fu,Xiaoyan Hu,Wei Chen,Fan Yang,Jiang Zhao,Qingqing Wang,Zhenqiang Fang,Longkun Li,Xiaobing Liu

doi:10.18632/oncotarget.21706

Qingjian Wu, Zhenxing Yang + Show 9 more

Open Access

https://doi.org/10.18632/oncotarget.21706

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Journal: Oncotarget	Publication Date: Oct 9, 2017
Citations: 27	License type: cc-by

Affiliation: Army Medical University

Abstract

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is up-regulated in various human cancers, and our results indicated that PVT1 was up-regulated in clear cell renal cell carcinoma tissues. The Cancer Genome Atlas cohort analysis revealed that in clear cell renal cell carcinoma, higher PVT1 expression correlated with advanced TNM stage, histological grade, and poor survival. PVT1 knockdown promoted apoptosis, inhibited renal cancer cell proliferation, decreased Mcl-1, and increased cleaved caspase-3 and cleaved PARP. PVT1 increased Mcl-1 mRNA levels in renal cancer cells by promoting mRNA stability without influencing its transcription. in vitro, the enhanced apoptosis arising from PVT1 suppression was attenuated by overexpressing Mcl-1. In addition, in vivo experiments showed that PVT1 knockdown repressed xenograft tumor growth, while Mcl-1 overexpression partially rescued xenograft tumor growth. These results indicate the PVT1/Mcl-1 pathway inhibits renal cancer cell apoptosis in vitro and in vivo. PVT1 may thus serve as a novel biomarker, and the PVT1/Mcl-1 pathway may be a useful therapeutic target for clear cell renal cell carcinoma.

Highlights

Renal cell carcinoma (RCC) is the most common malignant neoplasm of the kidney, which accounts for 2-3% of all adult malignancies [1]
Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is upregulated in various human cancers, and our results indicated that PVT1 was upregulated in clear cell renal cell carcinoma tissues
Compared with corresponding adjacent non-tumor tissues, PVT1 was up-regulated in 85.45% (47 of 55) of Clear cell renal cell carcinoma (CCRCC) tissues according to qRT-PCR (Figure 1A)

Summary

Introduction

Renal cell carcinoma (RCC) is the most common malignant neoplasm of the kidney, which accounts for 2-3% of all adult malignancies [1]. The incidence and mortality rate of RCC has increased in recent years, especially in young patients and those with high-grade disease [2, 3]. Due to the lack of early detection and RCC prognostic markers, 25%-30% of patients have already developed metastases at the time of diagnosis. Radical nephrectomy is the principal and most effective treatment for RCC, but more than 40% of patients develop metastases after radical nephrectomy with poor prognosis [5]. Clear cell renal cell carcinoma (CCRCC) is the most common and most aggressive histologic subtype of RCC, which accounts for 75%–80% of RCC [6].

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