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长链基因间非编码RNA 1547作为一种竞争性内源性RNA,通过靶向微小RNA-195-5p/同源盒C8轴在非小细胞肺癌中发挥促癌作用。

Long intergenic non-protein-coding RNA 1547 acts as a competing endogenous RNA and exerts cancer-promoting activity in non-small cell lung cancer by targeting the microRNA-195-5p/ homeobox C8 axis.

作者信息

Wu Wenjie, Zhu Siyu, Wu Yonghui, Dai Lu, Zhao Jian, Jiang Zeyong

机构信息

Department of Chest Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China.

Baiyun Lake Community Health Service Center of Baiyun District, Guangzhou 510450, China.

出版信息

Heliyon. 2023 Jul 26;9(8):e18015. doi: 10.1016/j.heliyon.2023.e18015. eCollection 2023 Aug.

Abstract

Long intergenic non-protein coding RNA 1547 (LINC01547) presents a notable relationship with prognosis in patients with ovarian cancer. Herein, we examined the expression of LINC01547 in non-small cell lung cancer (NSCLC) to ascertain its clinical significance. We also explored the detailed functions of LINC01547 in regulating the aggressive phenotype of NSCLC and the molecular mechanism of action underlying its carcinogenic activities events in NSCLC. Furthermore, we applied the data acquired from the tissue specimens and the Cancer Genome Atlas (TCGA) database to analyze the level of LINC01547 in NSCLC and conducted functional assays to address the regulatory effect of LINC01547. Further, we examined the mechanistic interaction among LINC01547, microRNA-195-5p (miR-195-5p), and homeobox C8 (HOXC8) using bioinformatics prediction and luciferase reporter assay. LINC01547 was noticeably overexpressed, as affirmed by data from TCGA and our own cohort; moreover, poor prognosis was associated with increased LINC01547 levels in patients with NSCLC. LINC01547 regulates cell proliferation, colony-forming, migration, and invasion, and its absence produced tumor-repressing effects in NSCLC. Mechanistically, as a competitive endogenous RNA, LINC01547 decoyed miR-195-5p and consequently resulted in the overexpression of HOXC8 in NSCLC cells. Using rescue experiments, we found that the regulatory activities of LINC01547 deficient in repressing the malignant properties of NSCLC cells could be counteracted by hindering miR-195-5p or overexpressing HOXC8. Conclusively, LINC01547 serves as a crucial component to worsen the oncogenicity of NSCLC cells by controlling the miR-195-5p/HOXC8 axis. Thus, the newly identified competing endogenous RNA pathway may potentially be an attractive therapeutic for NSCLC management.

摘要

长链基因间非编码RNA 1547(LINC01547)与卵巢癌患者的预后存在显著关联。在此,我们检测了LINC01547在非小细胞肺癌(NSCLC)中的表达,以确定其临床意义。我们还探究了LINC01547在调节NSCLC侵袭性表型中的详细功能及其致癌活性事件背后的分子作用机制。此外,我们运用从组织标本和癌症基因组图谱(TCGA)数据库获取的数据,分析了NSCLC中LINC01547的水平,并进行了功能试验以研究LINC01547的调节作用。进一步地,我们通过生物信息学预测和荧光素酶报告基因检测,研究了LINC01547、微小RNA - 195 - 5p(miR - 195 - 5p)和同源盒C8(HOXC8)之间的机制性相互作用。正如TCGA和我们自己队列的数据所证实的,LINC01547明显过表达;此外,NSCLC患者中LINC01547水平升高与预后不良相关。LINC01547调节细胞增殖、集落形成、迁移和侵袭,其缺失在NSCLC中产生肿瘤抑制作用。从机制上讲,作为一种竞争性内源性RNA,LINC01547诱捕miR - 195 - 5p,从而导致NSCLC细胞中HOXC8过表达。通过拯救实验,我们发现抑制NSCLC细胞恶性特性的LINC01547的调节活性可通过阻碍miR - 195 - 5p或过表达HOXC8来抵消。总之,LINC01547通过控制miR - 195 - 5p/HOXC8轴,成为恶化NSCLC细胞致癌性的关键因素。因此,新发现的竞争性内源性RNA途径可能是NSCLC治疗的一个有吸引力的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/10407678/52b72ae79da9/gr1.jpg

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