Yang Rui, Li Ping, Zhang Guojun, Lu Chunya, Wang Huaqi, Zhao Guoqiang
Department of Respiratory Medicine, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Cell Physiol Biochem. 2017;42(1):126-136. doi: 10.1159/000477121. Epub 2017 May 12.
The therapy and prognosis of lung cancer are difficult because of multiple genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) have been verified as new mediators of cancer development and progression by virtue of their various functions. Here, we focused on the lncRNA XLOC_008466 based on previous microarray data. However, whether aberrant expression of XLOC_008466 in human non-small cell lung cancer (NSCLC) is correlated with malignancy, metastasis or prognosis has not been elucidated.
We performed real-time PCR, CCK-8, flow cytometry, trans-well, western blotting, luciferase reporter assays, RNA immunoprecipitation (RIP) assay and surface plasmon resonance (SPR) assay to detect the function of XLOC_008466 in NSCLC.
Up-regulation of XLOC_008466 in NSCLC patients was related to lymph node metastasis and the TNM stage. In vitro, down-regulation of XLOC_008466 inhibited cell proliferation and invasion of A549 and H460 cells in vitro, but promoted cell apoptosis. Experiments on mechanisms revealed that XLOC_008466 functioned as a ceRNA, directly binding to miR-874, and could affect cell proliferation, apoptosis and invasion through regulation of miR-874 expression as well as by increasing matrix metalloproteinase 2 (MMP2) and X-linked inhibitor of apoptosis (XIAP) expression.
XLOC_008466 functions as an oncogene in NSCLC by regulating the miR-874-MMP2/XIAP axis, which indicates that XLOC_008466 may be a useful marker and potential therapeutic target in NSCLC.
由于多种基因和表观遗传改变，肺癌的治疗和预后颇具难度。长链非编码RNA（lncRNA）凭借其多种功能已被证实为癌症发生和发展的新介质。在此，基于先前的微阵列数据，我们聚焦于lncRNA XLOC_008466。然而，XLOC_008466在人类非小细胞肺癌（NSCLC）中的异常表达是否与恶性肿瘤、转移或预后相关尚未阐明。
我们进行了实时PCR、CCK-8、流式细胞术、Transwell实验、蛋白质印迹、荧光素酶报告基因检测、RNA免疫沉淀（RIP）检测和表面等离子体共振（SPR）检测，以检测XLOC_008466在NSCLC中的功能。
NSCLC患者中XLOC_008466的上调与淋巴结转移和TNM分期相关。在体外，XLOC_008466的下调抑制了A549和H460细胞的体外增殖和侵袭，但促进了细胞凋亡。机制实验表明，XLOC_008466作为一种竞争性内源RNA（ceRNA），直接与miR-874结合，并可通过调节miR-874的表达以及增加基质金属蛋白酶2（MMP2）和X连锁凋亡抑制蛋白（XIAP）的表达来影响细胞增殖、凋亡和侵袭。
XLOC_008466通过调节miR-874-MMP2/XIAP轴在NSCLC中发挥癌基因作用，这表明XLOC_008466可能是NSCLC中一个有用的标志物和潜在的治疗靶点。
