Lai I-Lu, Yang Chin-An, Lin Pei-Chin, Chan Wen-Ling, Lee Ya-Ting, Yen Ju-Chen, Chang Ya-Sian, Chang Jan-Gowth
Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan.
Department of Bioinformatics and Medical Enginerring, Asia University, Taichung, Taiwan.
Oncotarget. 2017 Oct 3;8(58):98148-98162. doi: 10.18632/oncotarget.21465. eCollection 2017 Nov 17.
Long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis. Myocardial infarction-associated transcript (MIAT), originally isolated as a candidate gene for myocardial infarction, has been found to act as an oncogene in chronic lymphocytic leukaemias and neuroendocrine prostate cancer (NEPC); however, little is known about its expression pattern, biological function, and underlying mechanism in non-small cell lung cancer (NSCLC). In this study, we observed that MIAT expression was upregulated in NSCLC, and its overexpression was associated with advanced tumor stage. Moreover, MIAT knockdown decreased cell proliferation, migration, invasion, and cell cycle arrested in G1 phase. Mechanistic investigation revealed that MIAT could interact with histone methyltransferase mixed-lineage leukemia (MLL). MIAT silencing impeded the binding of MLL on the matrix metalloproteinase 9 (MMP9) promoter region and epigenetically reduced MMP9 transcriptional activity. Overall, our findings suggest that MIAT expression is associated with NSCLC and may be one of the critical targets in progression and metastasis in NSCLC.
长链非编码RNA（lncRNAs）在肿瘤发生过程中发挥着关键作用。心肌梗死相关转录本（MIAT）最初作为心肌梗死的候选基因被分离出来，现已发现它在慢性淋巴细胞白血病和神经内分泌前列腺癌（NEPC）中作为一种癌基因发挥作用；然而，关于其在非小细胞肺癌（NSCLC）中的表达模式、生物学功能及潜在机制，人们所知甚少。在本研究中，我们观察到MIAT在NSCLC中表达上调，且其过表达与肿瘤晚期相关。此外，MIAT敲低可降低细胞增殖、迁移、侵袭能力，并使细胞周期阻滞在G1期。机制研究表明，MIAT可与组蛋白甲基转移酶混合谱系白血病（MLL）相互作用。MIAT沉默会阻碍MLL与基质金属蛋白酶9（MMP9）启动子区域的结合，并在表观遗传上降低MMP9的转录活性。总体而言，我们的研究结果表明，MIAT表达与NSCLC相关，可能是NSCLC进展和转移的关键靶点之一。
