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miRNA-577 通过直接靶向同源盒蛋白 A1 抑制非小细胞肺癌细胞的增殖和侵袭。

microRNA‑577 inhibits cell proliferation and invasion in non‑small cell lung cancer by directly targeting homeobox A1.

机构信息

Department of Gastrointestinal Medicine, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

Jilin Entry‑Exit Inspection and Quarantine Bureau, Changchun, Jilin 130062, P.R. China.

出版信息

Mol Med Rep. 2019 Mar;19(3):1875-1882. doi: 10.3892/mmr.2019.9804. Epub 2019 Jan 2.

DOI:10.3892/mmr.2019.9804
PMID:30628697
Abstract

An increasing number of studies have indicated that the dysregulation of microRNAs (miRNAs/miR) is closely associated with non‑small cell lung cancer (NSCLC) development and progression by acting as tumor suppressors or oncogenes. Therefore, an in‑depth understanding of the biological roles of miRNAs in NSCLC may provide novel therapeutic methods for the treatment of patients with this disease. In the present study, reverse transcription‑quantitative polymerase chain reaction was used to detect miR‑577 expression in NSCLC tissues and cell lines. Cell Counting Kit‑8 and Transwell invasion assays were performed to determine the effects of miR‑577 on NSCLC cell proliferation and invasion. Luciferase reporter assays were used to demonstrate the relationship between miR‑577 and homeobox A1 (HOXA1) in NSCLC cells. The results revealed that miR‑577 was markedly downregulated in NSCLC tissues and cell lines. Additionally, restoration of miR‑577 expression significantly decreased the proliferation and invasion of NSCLC cells. Furthermore, miR‑577 negatively regulated HOXA1 expression in NSCLC cells by directly binding to its 3'‑untranslated region. HOXA1 was significantly upregulated in NSCLC tissues, and its upregulation was inversely correlated with miR‑577. Notably, restored HOXA1 expression abrogated the reduced proliferation and invasion of NSCLC cells caused by miR‑577 overexpression. Taken together, these results indicated that miR‑577 may have served tumor suppressive roles in NSCLC by directly targeting HOXA1. Therefore, this miRNA may be developed as a potential therapeutic target for the therapy of patients with NSCLC.

摘要

越来越多的研究表明,microRNAs(miRNAs/miR)的失调通过作为肿瘤抑制因子或癌基因与非小细胞肺癌(NSCLC)的发生和发展密切相关。因此,深入了解miRNAs 在 NSCLC 中的生物学作用可能为治疗这种疾病的患者提供新的治疗方法。在本研究中,采用逆转录-定量聚合酶链反应检测 NSCLC 组织和细胞系中 miR-577 的表达。通过细胞计数试剂盒-8 和 Transwell 侵袭实验检测 miR-577 对 NSCLC 细胞增殖和侵袭的影响。通过荧光素酶报告基因实验证明 miR-577 与 NSCLC 细胞中同源盒 A1(HOXA1)之间的关系。结果表明,miR-577 在 NSCLC 组织和细胞系中明显下调。此外,恢复 miR-577 的表达显著降低了 NSCLC 细胞的增殖和侵袭。此外,miR-577 通过直接结合其 3'非翻译区负调控 NSCLC 细胞中 HOXA1 的表达。HOXA1 在 NSCLC 组织中明显上调,其上调与 miR-577 呈负相关。值得注意的是,恢复 HOXA1 的表达可消除 miR-577 过表达导致的 NSCLC 细胞增殖和侵袭减少。综上所述,这些结果表明 miR-577 可能通过直接靶向 HOXA1 在 NSCLC 中发挥肿瘤抑制作用。因此,这种 miRNA 可能被开发为治疗 NSCLC 患者的潜在治疗靶点。

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