RNAa and Vector-Mediated Overexpression of DIRAS1 Suppresses Tumor Growth and Migration in Renal Cell Carcinoma

Xin Xu; Jiangfeng Li; Song Wang; Xiangyi Zheng; Liping Xie

doi:10.1016/j.omtn.2018.07.019

RNAa and Vector-Mediated Overexpression of DIRAS1 Suppresses Tumor Growth and Migration in Renal Cell Carcinoma

Mol Ther Nucleic Acids. 2018 Sep 7:12:845-853. doi: 10.1016/j.omtn.2018.07.019. Epub 2018 Aug 8.

Authors

Xin Xu¹, Jiangfeng Li², Song Wang², Xiangyi Zheng², Liping Xie³

Affiliations

¹ Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China. Electronic address: drxuxin@zju.edu.cn.
² Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
³ Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China. Electronic address: xielp@zju.edu.cn.

Abstract

The downregulation of DIRAS1 has been suggested to potentially contribute to tumor development and progression in several human cancers. However, the role of DIRAS1 in renal cell carcinoma (RCC) remains elusive. In this study, we examined the DIRAS1 expression level in RCC cell lines and tissues. Both RNA activation (RNAa) and vector transfection methods were used to upregulate the expression of DIRAS1 in RCC cells. Expression analysis revealed that DIRAS1 was significantly downregulated in RCC cell lines and tissues compared with nontumorigenic renal cells and adjacent nontumor tissues individually. Promoter methylation analysis indicated that the reduced DIRAS1 expression might be partly mediated by epigenetic modulation. The RNAa-mediated overexpression of DIRAS1 inhibited cell proliferation and tumorigenicity in vitro and in vivo. The re-activation of DIRAS1 also promoted apoptosis and suppressed migration and invasion in RCC cells. The ectopic expression of DIRAS1 via an expression vector recapitulated the RNAa results. These results reveal that DIRAS1, functioning as a putative tumor suppressor in RCC cells, could potentially be a therapeutic target and RNAa could be a therapeutic strategy for RCC.

Keywords: DIRAS1; RNAa; apoptosis; proliferation; renal cell carcinoma.