Zhang Yixiang, Wang Yanjun, Wang Jinguang
Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
Department of Thoracic Surgery, Dalian University Affiliated Xinhua Hospital, Dalian, Liaoning 116011, P.R. China.
Exp Ther Med. 2018 Feb;15(2):2203-2211. doi: 10.3892/etm.2017.5624. Epub 2017 Dec 12.
Lung cancer is the third most frequent human malignant tumour and the leading cause of cancer-associated mortality worldwide. Emerging lines of evidence have demonstrated that microRNAs (miRNAs) are upregulated or downregulated in non-small cell lung cancer (NSCLC), and this phenomenon is involved in the regulation of various processes during tumorigenesis and progression, including tumour groWTh, apoptosis, cell invasion, and tumour metastasis. Therefore, understanding the molecular mechanism that associates abnormally expressed miRNAs with NSCLC formation and development may lead to the identification of novel diagnostic, and therapeutic targets for patients with NSCLC. miRNA-584 (miR-584) functions as a tumour suppressor in several types of cancer. However, the expression pattern, detailed biological function and underlying molecular mechanism of miR-584 in NSCLC remain unclear. Therefore, the present study detected the expression of miR-584 in NSCLC, investigated its role in NSCLC cells and determined its underlying molecular mechanism. In the current study, it was demonstrated that miR-584 was downregulated in NSCLC tissues and cell lines. Low miR-584 expression was correlated with tumour size, tumour node metastasis stage and distant metastasis. Overexpression of miR-584 inhibited cell proliferation and invasion in NSCLC. Additionally, metadherin was identified as a direct target gene of miR-584 in NSCLC as confirmed by a series of experiments. Moreover, upregulation of miR-584 was involved in the regulation of the phosphatase and tensin homolog/Akt serine/threonine kinase signalling pathway in NSCLC. Thus, miR-584 may serve as a tumor-suppressor, and the results of the present study provide a reference for future research into the potential mechanisms underlying NSCLC progression.
肺癌是人类第三常见的恶性肿瘤，也是全球癌症相关死亡的主要原因。越来越多的证据表明，微小RNA（miRNA）在非小细胞肺癌（NSCLC）中表达上调或下调，这种现象参与了肿瘤发生和发展过程中的各种调节过程，包括肿瘤生长、凋亡、细胞侵袭和肿瘤转移。因此，了解异常表达的miRNA与NSCLC形成和发展相关的分子机制，可能有助于识别NSCLC患者的新型诊断和治疗靶点。miRNA-584（miR-584）在几种类型的癌症中发挥肿瘤抑制作用。然而，miR-584在NSCLC中的表达模式、详细生物学功能和潜在分子机制仍不清楚。因此，本研究检测了miR-584在NSCLC中的表达，研究了其在NSCLC细胞中的作用，并确定了其潜在的分子机制。在当前研究中，结果表明miR-584在NSCLC组织和细胞系中表达下调。miR-584低表达与肿瘤大小、肿瘤淋巴结转移分期和远处转移相关。miR-584过表达抑制NSCLC细胞的增殖和侵袭。此外，通过一系列实验证实，metadherin被确定为NSCLC中miR-584的直接靶基因。此外，miR-584的上调参与了NSCLC中磷酸酶和张力蛋白同源物/蛋白激酶B信号通路的调节。因此，miR-584可能作为一种肿瘤抑制因子，本研究结果为进一步研究NSCLC进展的潜在机制提供了参考。
