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长链非编码 RNA 00174 通过 microRNA-185-5p/核因子 IX 轴加重肺鳞状细胞癌进展。

Long Intergenic Nonprotein Coding RNA 00174 Aggravates Lung Squamous Cell Carcinoma Progression via MicroRNA-185-5p/Nuclear Factor IX axis.

机构信息

Department of Thoracic Surgery, The No. 4 Hospital, No. 50 Shifan Road, Tianqiao District, Jinan, 250000 Shandong, China.

出版信息

Biomed Res Int. 2022 Aug 25;2022:9490827. doi: 10.1155/2022/9490827. eCollection 2022.

Abstract

Extensive studies have presented that long noncoding RNAs (lncRNAs) are closely implicated in the pathogenesis of various human malignancies, including lung squamous cell carcinoma (LUSC). This study explored the biological role and the underlying mechanism of long intergenic nonprotein coding RNA 00174 (LINC00174) in LUSC. LINC00174 expression was measured by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Both in vitro and in vivo experiments were conducted to determine LINC00174 function in LUSC. Mechanical assays were performed to investigate the molecular mechanism involving LINC00174 and related genes. LINC00174 expression was high in LUSC cells. Silencing of LINC00174 could restrain LUSC cells proliferation, migration, and invasion while promoting cell apoptosis. Mechanically, LINC00174 could interact with miR-185-5p to upregulate nuclear factor IX (NFIX), which was the direct target gene of miR-185-5p. Notably, NFIX elevation could rescue the repressing effect of LINC00174 silence on LUSC cell malignant behaviors. Our data suggested that LINC00174 aggravated LUSC progression via serving as a competing endogenous RNA (ceRNA) to sponge miR-185-5p and ultimately upregulate NFIX, which offered a promising novel target for LUSC therapy.

摘要

大量研究表明,长链非编码 RNA(lncRNAs)与包括肺鳞状细胞癌(LUSC)在内的多种人类恶性肿瘤的发病机制密切相关。本研究探讨了长基因间非蛋白编码 RNA 00174(LINC00174)在 LUSC 中的生物学作用及其潜在机制。通过逆转录定量实时聚合酶链反应(RT-qPCR)测量 LINC00174 的表达。进行了体外和体内实验以确定 LINC00174 在 LUSC 中的功能。通过机械测定来研究涉及 LINC00174 和相关基因的分子机制。LINC00174 在 LUSC 细胞中表达较高。沉默 LINC00174 可抑制 LUSC 细胞的增殖、迁移和侵袭,同时促进细胞凋亡。从机制上讲,LINC00174 可以与 miR-185-5p 相互作用,从而上调核因子 IX(NFIX),NFIX 是 miR-185-5p 的直接靶基因。值得注意的是,NFIX 水平的升高可以挽救 LINC00174 沉默对 LUSC 细胞恶性行为的抑制作用。我们的数据表明,LINC00174 通过作为竞争性内源性 RNA(ceRNA)来吸附 miR-185-5p 并最终上调 NFIX,从而加重 LUSC 进展,为 LUSC 治疗提供了有前途的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d42/9436563/66b35f1a20a3/BMRI2022-9490827.001.jpg

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