Liu Gaofeng, Zhang Yong, Zhang Xiaozhen, Liu Yan, Xu Yanbin, Cui Sujuan, Li Gang, Wang Jianjun
Department of Cardiothoracic Surgery, The 988th Hospital of PLA Joint Logistics Support Zhengzhou 450042, Henan, China.
Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University Zhengzhou 450008, Henan, China.
Am J Transl Res. 2022 Jul 15;14(7):4977-4989. eCollection 2022.
LncRNA MNX1-AS1 is known to be involved in progression of several tumor types. However, few studies have investigated the molecular mechanism of MNX1-AS1 in lung adenocarcinoma (LAC). To explore the function of MNX1-AS1 in the pathogenesis of LAC, qRT-PCR was performed to show MNX1-AS1 expression. MNX1-AS1 expression in LAC cells was suppressed by siRNA to detect the biologic behavior. The relationships among miR-34a, MNX1-AS1 and SIRT1 were confirmed by pull-down and dual-luciferase reporter assay. Whether MNX1-AS1 was involved in LAC by targeting miR-34a/SIRT1 axis was verified. MNX1-AS1 was up-regulated in LAC, and over-expression of MNX1-AS1 was significantly associated with lymph node metastasis and poor prognosis. In A549 and H1299 cells, cell proliferation, migration, and invasion were suppressed, the cell cycle was regulated, as well as apoptosis was increased after silencing MNX1-AS1. Mechanistically, MNX1-AS1 served as a ceRNA of miR-34a to down-regulate miR-34a expression. SIRT1 is targeted by miR-34a and its expression is regulated by MNX1-AS1 and miR-34a. Up-regulation of SIRT1 salvaged the effect of silencing MNX1-AS1 on A549 and H1299 cells, to some extent. These results showed that MNX1-AS1 contributes to LAC progression by targeting the miR-34a/SIRT1 axis.
已知长链非编码RNA MNX1-AS1参与多种肿瘤类型的进展。然而,很少有研究探讨MNX1-AS1在肺腺癌(LAC)中的分子机制。为了探究MNX1-AS1在LAC发病机制中的作用,进行了qRT-PCR以检测MNX1-AS1的表达。通过小干扰RNA(siRNA)抑制LAC细胞中MNX1-AS1的表达,以检测其生物学行为。通过下拉实验和双荧光素酶报告基因检测验证了miR-34a、MNX1-AS1和沉默调节蛋白1(SIRT1)之间的关系。验证了MNX1-AS1是否通过靶向miR-34a/SIRT1轴参与LAC的发生发展。MNX1-AS1在LAC中上调,其过表达与淋巴结转移及预后不良显著相关。在A549和H1299细胞中,沉默MNX1-AS1后,细胞增殖、迁移和侵袭受到抑制,细胞周期受到调控,同时细胞凋亡增加。机制上,MNX1-AS1作为miR-34a的竞争性内源RNA(ceRNA)下调miR-34a的表达。SIRT1是miR-34a的靶标,其表达受MNX1-AS1和miR-34a的调控。SIRT1的上调在一定程度上挽救了沉默MNX1-AS1对A549和H1299细胞的影响。这些结果表明,MNX1-AS1通过靶向miR-34a/SIRT1轴促进LAC的进展。