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DLEU7反义RNA1通过沉默miR-26a-5p/冠蛋白3轴促进肾细胞癌。

DLEU7-AS1 promotes renal cell cancer by silencing the miR-26a-5p/coronin-3 axis.

作者信息

Wang Xin-Jun, Chen Lin, Xu Ran, Li Si, Luo Guang-Cheng

机构信息

Department of Urology, Zhongshan Hospital Xiamen University, School of medicine, Xiamen University, Xiamen, Fujian, China.

The Third Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.

出版信息

Clin Kidney J. 2022 Feb 28;15(8):1542-1552. doi: 10.1093/ckj/sfac061. eCollection 2022 Aug.

DOI:10.1093/ckj/sfac061
PMID:35892027
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9308101/
Abstract

Long non-coding RNAs (lncRNAs) have been implicated in the progression and development of many types of cancer by interacting with RNA, DNA and proteins, including DLEU7-AS1. However, the function of DLEU7-AS1 in renal cell cancer (RCC) remains unclear. In this study, two prediction algorithms were used to discover the potential target of miR-26a-5p, which was determined to be a tumor suppressor gene, possibly DLEU7-AS1, through the downregulation of coronin-3 in RCC. Thus, we hypothesized that DLEU7-AS1 promotes RCC by silencing the miR-26a-5p/coronin-3 axis. To test our hypothesis, we confirmed that DLEU7-AS1 directly targets miR-26a-5p using the pmirGLO dual-luciferase reporter assay. Next, we observed that DLEU7-AS1 expression was markedly upregulated in RCC samples and inversely correlated with clinical prognosis and miR-26a-5p levels. Knockdown of DLEU7-AS1 significantly suppressed the growth and metastasis of RCC cells and attenuated tumor growth . Interestingly, exogenous expression of coronin-3 or miR-26a-5p inhibitor treatment almost completely rescued the DLEU7-AS1 knockdown-induced inhibitory effects on cell proliferation, migration and invasion. In conclusion, our data demonstrate that DLEU7-AS1 is an oncogene in RCC capable of regulating the growth and metastasis of RCC by silencing the miR-26a-5p/coronin-3 axis, suggesting that DLEU7-AS1 can be employed as a potential therapeutic target and prognostic biomarker for RCC.

摘要

长链非编码RNA（lncRNA）通过与RNA、DNA和蛋白质相互作用，参与了多种癌症的进展和发展，其中包括DLEU7-AS1。然而，DLEU7-AS1在肾细胞癌（RCC）中的功能仍不清楚。在本研究中，我们使用两种预测算法来发现miR-26a-5p的潜在靶点，通过RCC中coronin-3的下调，确定其为肿瘤抑制基因，可能是DLEU7-AS1。因此，我们假设DLEU7-AS1通过沉默miR-26a-5p/coronin-3轴促进RCC的发生发展。为了验证我们的假设，我们使用pmirGLO双荧光素酶报告基因检测法证实DLEU7-AS1直接靶向miR-26a-5p。接下来，我们观察到DLEU7-AS1在RCC样本中的表达明显上调，且与临床预后和miR-26a-5p水平呈负相关。敲低DLEU7-AS1可显著抑制RCC细胞的生长和转移，并减缓肿瘤生长。有趣的是，coronin-3的外源表达或miR-26a-5p抑制剂处理几乎完全挽救了DLEU7-AS1敲低对细胞增殖、迁移和侵袭的抑制作用。总之，我们的数据表明DLEU7-AS1是RCC中的一个癌基因，能够通过沉默miR-26a-5p/coronin-3轴来调节RCC的生长和转移，这表明DLEU7-AS1可作为RCC的潜在治疗靶点和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/1f6759b2b0e0/sfac061fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/28922288f281/sfac061fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/190c689e1658/sfac061fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/8c7531454beb/sfac061fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/4a2f4fabfde8/sfac061fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/e74fdc7caed6/sfac061fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/d6032fec1167/sfac061fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/1f6759b2b0e0/sfac061fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/28922288f281/sfac061fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/190c689e1658/sfac061fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/8c7531454beb/sfac061fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/4a2f4fabfde8/sfac061fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/e74fdc7caed6/sfac061fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/d6032fec1167/sfac061fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2584/9308101/1f6759b2b0e0/sfac061fig7.jpg

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