LncRNA DGCR5 Isoform-1 Silencing Suppresses the Malignant Phenotype of Clear Cell Renal Cell Carcinoma via miR-211-5p/Snail Signal Axis.

Guang-Xin Zhong,Xiang Zhang,Dan Luo,Zhong-Hua Xu,Jue Wang,Yi-Jun Fan,Bing-Qiang Liu

doi:10.3389/fcell.2021.700029

Abstract

Long non-coding RNAs (lncRNAs) play important roles during the initiation and progression of cancer. We identified DiGeorge Syndrome Critical Region Gene 5 (DGCR5) as a clear cell renal cell carcinoma (ccRCC) cancer- and lineage-specific lncRNA. Agarose gel electrophoresis analysis and sanger sequencing verified two main isoforms of DGCR5 in ccRCC patient tissues and cell lines. Quantitative polymerase chain reaction further demonstrated that the expression level of DGCR5 major isoform (isoform-1) was higher in ccRCC tissues than that in papillary/chromophobe RCC and other multiple solid malignant tumors. We investigate the biological functions of DGCR5 isoform-1 in ccRCC and show that DGCR5 isoform-1 exerts a tumor-promoting effect in ccRCC. DGCR5 isoform-1 is localized in cytoplasm and shares the same binding sequence to the tumor-suppressive miR-211-5p with the epithelial-to-mesenchymal transition key component SNAI. Furthermore, cellular and molecular experiments demonstrate that DGCR5 isoform-1 could sequester miR-211-5p, leading to the elevation of Snail protein and downregulation of its downstream targets and further promoting ccRCC cell proliferation and migration. Thus, our study indicates that DGCR5 isoform-1 could contribute to ccRCC progression by sponging miR-211-5p through regulating the expression of Snail protein and could serve as a reliable diagnostic biomarker in ccRCC.

Highlights

Clear cell renal cell carcinoma is the most common kidney cancer in adults and the most fatal cancer among all urinary malignant tumors (Bray et al, 2018; Siegel et al, 2018)
We focused on isoform-1 using primer set 3, which exclusively targets DiGeorge Syndrome Critical Region Gene 5 (DGCR5) isoform-1 (The fulllength sequence of isoform-1 is provided in Supplementary Figure 1C)
DGCR5 expression was very low in papillary RCC, liver cancer, and lung squamous cell carcinoma and rarely detected in chromophobe RCC, prostate cancer, and colon cancer (Figure 1D)

Summary

Introduction

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer in adults and the most fatal cancer among all urinary malignant tumors (Bray et al, 2018; Siegel et al, 2018). Our previous data mining and analysis of publicly available RNA sequencing data identified DiGeorge Syndrome Critical Region Gene 5 (DGCR5) as a ccRCC cancer- and lineage-specific expressed lncRNA, which highly expresses in ccRCC human tissues (Zhang et al, 2018). Recent studies show that DGCR5 plays important roles in various types of cancers in the lung (Chen et al, 2017; Dong et al, 2018; Luo et al, 2018; Wang R. et al, 2018), liver (Wang Y.G. et al, 2018; Wang et al, 2019), stomach (Xu et al, 2019), and bladder (Fang et al, 2019), among others. The biological role of DGCR5 in ccRCC, it is most highly expressed in ccRCC among the abovementioned cancer types, remains unclear

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Discussion

Conclusion