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长链非编码RNA SNHG3通过调控BIRC5表达促进肾透明细胞癌进展。

Long non-coding RNA SNHG3 promotes the progression of clear cell renal cell carcinoma via regulating BIRC5 expression.

作者信息

Xu Zhaoyu, Ye Junjie, Bao Pengfei, Wu Qi, Xie Fuchen, Li Peng

机构信息

Department of Urology, Lishui People's Hospital, Lishui, China.

出版信息

Transl Cancer Res. 2021 Oct;10(10):4502-4513. doi: 10.21037/tcr-21-1802.

Abstract

BACKGROUND

Research has shown that the progression of clear cell renal cell carcinoma (ccRCC) is modulated by long non-coding RNAs (lncRNAs). However, the roles of specific lncRNAs in the malignancy of ccRCC are still unknown.

METHODS

TCGA and GSE66272 datasets were used to predict differentially expressed genes (DEGs) in ccRCC. ENCORI database was employed to display BIRC5 miRNA network and potential lncRNA interactions for miRNAs. KM plotter and correlation analyses were performed to identify the overall survival (OS)- and BIRC5-related miRNAs. Quantitative real-time PCR (qRT-PCR) was used to verify the BIRC5 mRNA in the seventy paired clinical samples of ccRCC tissues. The ccRCC A498 and 786-O were individually transfected with lncRNA SNHG3 and LINC00997 and then western blotting was used to detect the BIRC5 protein expression. The Dual-luciferase reporter assay was used to examine the regulatory interaction between lncRNA SNHG3 and microRNA (miRNA/miR)-10b-5p.

RESULTS

BICR5 is associated with the progression of ccRCC. The two novel lncRNAs (LINC00997, SNHG3) were up-regulated in ccRCC tissues and positively with the BICR5 protein expression. However, Suppressing SNHG3 expression reduced BIRC5 protein expression compared with the LINC00997, most importantly, Suppressing SNHG3 expression suppressed tumor progression . In addition, SNHG3 promotes the expression of BIRC5 protein by sponging microRNA-10b-5p.

CONCLUSIONS

Our findings suggest that SNHG3 plays a vital role in promoting ccRCC via the microRNA-10b-5p/BIRC5 axis and may serve as a novel therapeutic target for the treatment of patients with ccRCC.

摘要

背景

研究表明,长链非编码RNA(lncRNA)可调节透明细胞肾细胞癌(ccRCC)的进展。然而,特定lncRNA在ccRCC恶性肿瘤中的作用仍不清楚。

方法

利用TCGA和GSE66272数据集预测ccRCC中的差异表达基因(DEG)。使用ENCORI数据库展示BIRC5 miRNA网络以及miRNA的潜在lncRNA相互作用。进行KM绘图和相关性分析以鉴定总生存期(OS)和与BIRC5相关的miRNA。采用定量实时PCR(qRT-PCR)验证70对ccRCC组织临床样本中的BIRC5 mRNA。分别用lncRNA SNHG3和LINC00997转染ccRCC A498和786-O细胞,然后用蛋白质免疫印迹法检测BIRC5蛋白表达。采用双荧光素酶报告基因测定法检测lncRNA SNHG3与微小RNA(miRNA/miR)-10b-5p之间的调控相互作用。

结果

BICR5与ccRCC的进展相关。两种新型lncRNA(LINC00997、SNHG3)在ccRCC组织中上调,且与BICR5蛋白表达呈正相关。然而,与LINC00997相比,抑制SNHG3表达可降低BIRC5蛋白表达,最重要的是,抑制SNHG3表达可抑制肿瘤进展。此外,SNHG3通过吸附微小RNA-10b-5p促进BIRC5蛋白表达。

结论

我们的研究结果表明,SNHG3通过微小RNA-10b-5p/BIRC5轴在促进ccRCC中起重要作用,可能成为治疗ccRCC患者的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cec/8798718/d064377fda4f/tcr-10-10-4502-f1.jpg

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