Department of Cancer Biotherapy, Shanxi Academy of Medical Sciences (Shanxi Dayi Hospital), Taiyuan 030032, China.
Department of Endoscopy, Shanxi Province Cancer Hospital, Taiyuan 030013, China.
Biomed Pharmacother. 2019 Jun;114:108847. doi: 10.1016/j.biopha.2019.108847. Epub 2019 Apr 7.
MALAT1 is well documented to be highly expressed in non-small cell lung cancer (NSCLC) and its overexpression closely associates the malignant phenotype of NSCLC cells and poor prognosis of NSCLC patients. MALAT1 is also identified to enhance β-catenin expression and under the negative regulation of miR-142-3p. However, the role of miR-142-3p/MALAT1/β-catenin in the occurrence and development of NSCLC remains unclear. The objective of this study was to explore it. The results showed that miR-142-3p expression was reduced in NSCLC tissues, while β-catenin and MALAT1 expression levels were elevated. MTT, transwell chamber, flow cytometry assays demonstrated that up-regulation of miR-142-3p with mimic transfection significantly inhibited the proliferation, migration and promoted the apoptosis of NSCLC H1299 cells, and induced a G0/G1 phase arrest and S phase reduction. Besides, miR-142-3p negatively decreased MALAT1 expression as detected by RT-PCR and luciferase reporter assays. Moreover, up-regulation of miR-142-3p decreased β-catenin expression through down-regulating MALAT1 in H1299 cells. And in vivo experiment showed that miR-142-3p up-regulation, as well as the knockdown of either β-catenin or MALAT1 significantly reduced the tumorigenesis of NSCLC cells. Taken together, our study makes clear that miR-142-3p functions as a tumor suppressor in NSCLC progression through inhibiting MALAT1/β-catenin signaling.
MALAT1 在非小细胞肺癌（NSCLC）中高度表达，其过表达与 NSCLC 细胞的恶性表型和 NSCLC 患者的不良预后密切相关。MALAT1 也被确定为增强β-catenin 的表达，并受 miR-142-3p 的负调控。然而，miR-142-3p/MALAT1/β-catenin 在 NSCLC 的发生和发展中的作用尚不清楚。本研究旨在探讨这一问题。结果表明，miR-142-3p 在 NSCLC 组织中的表达降低，而β-catenin 和 MALAT1 的表达水平升高。MTT、Transwell 室、流式细胞术实验表明，用 mimic 转染上调 miR-142-3p 可显著抑制 NSCLC H1299 细胞的增殖、迁移，并促进其凋亡，诱导 G0/G1 期阻滞和 S 期减少。此外，RT-PCR 和荧光素酶报告基因实验表明，miR-142-3p 负向降低 MALAT1 的表达。此外，在 H1299 细胞中上调 miR-142-3p 通过下调 MALAT1 降低β-catenin 的表达。体内实验表明，miR-142-3p 的上调以及β-catenin 或 MALAT1 的敲低均显著降低了 NSCLC 细胞的肿瘤发生。综上所述，我们的研究表明，miR-142-3p 通过抑制 MALAT1/β-catenin 信号通路在 NSCLC 进展中发挥肿瘤抑制作用。
