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Long noncoding RNA RBMS3-AS3 acts as a microRNA-4534 sponge to inhibit the progression of prostate cancer by upregulating VASH1.
Gene Therapy ( IF 4.6 ) Pub Date : 2019-11-11 , DOI: 10.1038/s41434-019-0108-1
Zhenming Jiang 1 , Yuxi Zhang 1, 2 , Xi Chen 3 , Pingeng Wu 1 , Dong Chen 4
Affiliation  

Long noncoding RNAs (lncRNAs) have been demonstrated to participate in the progression of many malignancies, including prostate cancer by serving as sponges of microRNAs (miRNAs). Initial microarray-based analysis screened out the poorly expressed lncRNA RBMS3-AS3 in prostate cancer, followed by the identification of putative binding sites with miR-4534 and its target VASH1. Therefore, the present study set out to investigate the potential role of RBMS3-AS3/miR-4534/VASH1 axis in the development of prostate cancer. The biological functions of RBMS3-AS3, miR-4534, and VASH1 on cell proliferation, migration, invasion, and angiogenesis of prostate cancer were evaluated via gain- and loss-of-function experiments. Furthermore, tumor xenograft in nude mice was performed to examine tumorigenesis in vivo. The obtained results indicated that RBMS3-AS3 was poorly expressed in prostate cancer tissues and cells. Of note, overexpression of RBMS3-AS3 was found to suppress cell proliferation, migration, invasion, and angiogenesis as well as the tumorigenic ability of prostate cancer. VASH1 was verified as a target gene of miR-4534. VASH1 expression was found to be downregulated in prostate cancer tissues and cells. Interestingly, RBMS3-AS3 was observed to competitively bind to miR-4534 to upregulate VASH1 expression, resulting in a suppressive role in prostate cancer development. Also, in vitro findings were reproduced in vivo on tumor xenograft in nude mice. Taken together, the present study provides evidence suggesting that RBMS3-AS3 acts as a miR-4534 sponge to inhibit the development of prostate cancer by upregulating VASH1, highlighting a theoretical target for prostate cancer treatment.

中文翻译:


长非编码 RNA RBMS3-AS3 作为 microRNA-4534 海绵,通过上调 VASH1 抑制前列腺癌的进展。



长非编码 RNA (lncRNA) 已被证明可作为 microRNA (miRNA) 的海绵参与许多恶性肿瘤的进展,包括前列腺癌。最初基于微阵列的分析筛选出了前列腺癌中表达较差的 lncRNA RBMS3-AS3,随后鉴定了 miR-4534 及其靶标 VASH1 的假定结合位点。因此,本研究着手探讨 RBMS3-AS3/miR-4534/VASH1 轴在前列腺癌发生中的潜在作用。通过功能获得和丧失实验评估了 RBMS3-AS3、miR-4534 和 VASH1 对前列腺癌细胞增殖、迁移、侵袭和血管生成的生物学功能。此外,在裸鼠中进行肿瘤异种移植以检查体内肿瘤发生。所得结果表明RBMS3-AS3在前列腺癌组织和细胞中表达较差。值得注意的是,RBMS3-AS3 的过度表达被发现可以抑制细胞增殖、迁移、侵袭和血管生成以及前列腺癌的致瘤能力。 VASH1被验证为miR-4534的靶基因。发现前列腺癌组织和细胞中 VASH1 表达下调。有趣的是,观察到 RBMS3-AS3 竞争性地结合 miR-4534,上调 VASH1 表达,从而在前列腺癌发展中发挥抑制作用。此外,体外研究结果在裸鼠肿瘤异种移植物上得到了体内重现。总而言之,本研究提供的证据表明 RBMS3-AS3 作为 miR-4534 海绵,通过上调 VASH1 抑制前列腺癌的发展,强调了前列腺癌治疗的理论靶点。
更新日期:2019-11-11
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