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长链非编码RNA AGAP2-AS1沉默通过上调微小RNA-195-5p抑制PDLIM5表达,从而阻碍前列腺癌进展

Long Non-coding RNA AGAP2-AS1 Silencing Inhibits PDLIM5 Expression Impeding Prostate Cancer Progression Up-Regulation of MicroRNA-195-5p.

作者信息

Xie Pingbo, Liu Mingsheng, Chen Fen, Wu Shaomei, Shao Tao, Wang Wei, Xu Chenxiang, Zhou Hongqing

机构信息

The Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing, China.

出版信息

Front Genet. 2020 Sep 25;11:1030. doi: 10.3389/fgene.2020.01030. eCollection 2020.

Abstract

Prostate cancer remains a significant cause of cancer-related deaths in male population. More recently, accumulating evidence continues to implicate long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in various types of cancers, including prostate cancer. The current study aimed to elucidate the role of lncRNA AGAP2-AS1/miR-195-5p/PDZ and LIM domain 5 (PDLIM5) in prostate cancer progression. Initially, microarray expression profiles were applied to screen differentially expressed lncRNAs/miRNAs/genes associated with prostate cancer. Dual-luciferase reporter and RNA pull-down/RIP assays were subsequently performed to explore the interactions among lncRNA AGAP2-AS1, miR-195-5p, and PDLIM5, after which their expression was detected in cancer tissues and cells. Next, gain- and loss-of-function approaches were employed to elucidate the mechanism of lncRNA AGAP2-AS1/miR-195-5p/PDLIM5 in the processes of cell proliferation, migration and invasion as well as tumor growth. LncRNA AGAP2-AS1 was found to be highly expressed in prostate cancer. Silencing of lncRNA AGAP2-AS1 contributed to the suppression of proliferation, migration and invasion of cancer cells . Besides, lncRNA AGAP2-AS1 could bind to miR-195-5p which targeted PDLIM5 and subsequently downregulated its expression, ultimately impeding the progression of prostate cancer. Additionally, lncRNA AGAP2-AS1 inhibition led to an up-regulated expression of miR-195-5p and down-regulated PDLIM5 expression, resulting in delayed tumor growth . Taken together, the key findings of our study demonstrated that lncRNA AGAP2-AS1 silencing exerted suppressive effects on the development of prostate cancer via the miR-195-5p-dependent downregulation of PDLIM5. Our findings highlighted the potential of lncRNA AGAP2-AS1 as a promising novel molecular target for prostate cancer therapy.

摘要

前列腺癌仍然是男性人群中癌症相关死亡的一个重要原因。最近,越来越多的证据继续表明长链非编码RNA(lncRNAs)、微小RNA(miRNAs)和信使RNA(mRNAs)在包括前列腺癌在内的各种类型癌症中发挥作用。当前的研究旨在阐明lncRNA AGAP2-AS1/miR-195-5p/PDZ和LIM结构域5(PDLIM5)在前列腺癌进展中的作用。最初,应用微阵列表达谱来筛选与前列腺癌相关的差异表达lncRNAs/miRNAs/基因。随后进行双荧光素酶报告基因检测以及RNA下拉/RIP实验,以探究lncRNA AGAP2-AS1、miR-195-5p和PDLIM5之间的相互作用,之后检测它们在癌组织和细胞中的表达。接下来,采用功能获得和功能缺失方法来阐明lncRNA AGAP2-AS1/miR-195-5p/PDLIM5在细胞增殖、迁移和侵袭以及肿瘤生长过程中的作用机制。研究发现lncRNA AGAP2-AS1在前列腺癌中高表达。沉默lncRNA AGAP2-AS1有助于抑制癌细胞的增殖、迁移和侵袭。此外,lncRNA AGAP2-AS1可以与靶向PDLIM5的miR-195-5p结合,随后下调其表达,最终阻碍前列腺癌的进展。此外,抑制lncRNA AGAP2-AS1会导致miR-195-5p表达上调以及PDLIM5表达下调,从而延缓肿瘤生长。综上所述,我们研究的关键发现表明,lncRNA AGAP2-AS1沉默通过miR-195-5p依赖的方式下调PDLIM5,对前列腺癌的发展发挥抑制作用。我们的研究结果突出了lncRNA AGAP2-AS1作为前列腺癌治疗有前景的新型分子靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc87/7546420/43742326aea6/fgene-11-01030-g001.jpg

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