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长链非编码RNA UCA1通过海绵化微小RNA-495调控PRL-3表达以促进胃癌进展。

Long Noncoding RNA UCA1 Regulates PRL-3 Expression by Sponging MicroRNA-495 to Promote the Progression of Gastric Cancer.

作者信息

Cao Yi, Xiong Jian-Bo, Zhang Guo-Yang, Liu Yi, Jie Zhi-Gang, Li Zheng-Rong

机构信息

Department of Gastroenterological Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R. China.

Department of Gastroenterological Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R. China.

出版信息

Mol Ther Nucleic Acids. 2020 Mar 6;19:853-864. doi: 10.1016/j.omtn.2019.10.020. Epub 2019 Oct 25.

Abstract

Gastric cancer (GC) is among the most frequently occurring malignancies worldwide. In recent years, long noncoding RNAs (lncRNAs) have been widely studied because of their ability to regulate the cellular processes involved with tumorigenesis. The present study aims to investigate the underlying molecular mechanism by which lncRNA urothelial carcinoma-associated 1 (UCA1) influences the progression of GC. Differentially expressed lncRNA UCA1 was initially identified by microarray-based analysis, after which a high expression of UCA1 was determined in GC tissues and cells. It is important to note that UCA1 could upregulate the expression of phosphatase of regenerating liver-3 (PRL-3) by sponging miR-495. The expression of UCA1 and miR-495 was altered in human GC cells to evaluate cell activity in vitro, as well as peritoneal metastasis and tumor formation ability in vivo. Results suggested that increased expression of UCA1 promoted cell proliferation, migration, and invasion, accompanied by suppressed cell apoptosis, as well as enhanced peritoneal metastasis and tumorigenesis of GC cells. Meanwhile, the upregulated expression of miR-495 could reverse the promotive effects exerted by UCA1. Taken conjointly, UCA1, as a competing endogenous RNA (ceRNA) of miR-495, could accelerate the development of GC by upregulating PRL-3, highlighting a potentially promising basis for the targeted intervention treatment of GC.

摘要

胃癌(GC)是全球最常见的恶性肿瘤之一。近年来,长链非编码RNA(lncRNA)因其能够调节与肿瘤发生相关的细胞过程而受到广泛研究。本研究旨在探讨lncRNA尿路上皮癌相关1(UCA1)影响GC进展的潜在分子机制。通过基于微阵列的分析初步鉴定出差异表达的lncRNA UCA1,随后确定其在GC组织和细胞中高表达。值得注意的是,UCA1可通过吸附miR-495上调再生肝磷酸酶3(PRL-3)的表达。在人GC细胞中改变UCA1和miR-495的表达,以评估体外细胞活性以及体内腹膜转移和肿瘤形成能力。结果表明,UCA1表达增加促进细胞增殖、迁移和侵袭,同时抑制细胞凋亡,并增强GC细胞的腹膜转移和肿瘤发生。同时,miR-495表达上调可逆转UCA1发挥的促进作用。综上所述,UCA1作为miR-495的竞争性内源RNA(ceRNA),可通过上调PRL-3加速GC的发展,为GC的靶向干预治疗提供了潜在的有前景的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bea/6992896/b747f9064a49/fx1.jpg

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