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长非编码 RNA UFC1 通过调节 miR-498/Lin28b 促进胃癌进展。

Long non-coding RNA UFC1 promotes gastric cancer progression by regulating miR-498/Lin28b.

机构信息

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.

Institute of Digestive Diseases of Jiangsu University, The Affiliated People's Hospital of Jiangsu University, 8 Dianli Road, Zhenjiang, 212002, Jiangsu, China.

出版信息

J Exp Clin Cancer Res. 2018 Jul 3;37(1):134. doi: 10.1186/s13046-018-0803-6.

Abstract

BACKGROUND

Long non-coding RNAs (lncRNAs) have emerged as important regulators of human cancers. However, the functional roles of lncRNAs and the mechanisms responsible for their aberrant expression in gastric cancer (GC) have not been well characterized.

METHODS

In this study, we examined the expression of lncRNA UFC1 in GC by qRT-PCR and explored its correlation with clinicopathological parameters. In vitro cell functional assays and in vivo animal studies were performed to determine the roles of UFC1 in GC progression.

RESULTS

UFC1 was elevated and predicted poorer prognosis in GC. UFC1 knockdown inhibited while UFC1 overexpression promoted GC cell proliferation, migration, and invasion. UFC1 bound to miR-498 to antagonize its tumor suppressive effect on Lin28b. Suppression of Lin28b by miR-498 could be rescued by UFC1 overexpression, whereas Lin28b overexpression partially rescued UFC1 knockdown-mediated inhibition of GC cell function. Lin28b expression was increased in GC and suggested a co-expression pattern with UFC1.

CONCLUSIONS

UFC1 has a promoting role in GC progression, at least in part, by acting as a miR-498 sponge and derepressing Lin28b expression, which would provide a novel biomarker for GC diagnosis and prognosis and offer a potential target for GC therapy.

摘要

背景

长链非编码 RNA(lncRNAs)已成为人类癌症的重要调控因子。然而,lncRNAs 的功能作用及其在胃癌(GC)中异常表达的机制尚未得到很好的描述。

方法

在这项研究中,我们通过 qRT-PCR 检测了 lncRNA UFC1 在 GC 中的表达,并探讨了其与临床病理参数的相关性。通过体外细胞功能测定和体内动物研究来确定 UFC1 在 GC 进展中的作用。

结果

UFC1 在 GC 中上调,并预测预后不良。UFC1 敲低抑制,而 UFC1 过表达促进 GC 细胞增殖、迁移和侵袭。UFC1 与 miR-498 结合,拮抗其对 Lin28b 的肿瘤抑制作用。miR-498 抑制 Lin28b 可被 UFC1 过表达挽救,而 Lin28b 过表达部分挽救了 UFC1 敲低介导的 GC 细胞功能抑制。GC 中 Lin28b 的表达增加,并提示与 UFC1 具有共同表达模式。

结论

UFC1 至少部分通过作为 miR-498 的海绵体和解除 Lin28b 的表达来促进 GC 进展,这将为 GC 的诊断和预后提供一个新的生物标志物,并为 GC 的治疗提供一个潜在的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62a6/6029056/10d8c9f2fa19/13046_2018_803_Fig1_HTML.jpg

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