MiR-142-3p suppresses the proliferation, migration and invasion through inhibition of NR2F6 in lung adenocarcinoma
MiR-142-3p suppresses the proliferation, migration and invasion through inhibition of NR2F6 in lung adenocarcinoma
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DOI：
10.1007/s13577-019-00258-0
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发表时间：
2019-10-01
期刊：
影响因子：
4.3
通讯作者：
Ren, Shuhua
中科院分区：
文献类型：
--
作者：
Jin, Chang'e;Xiao, Liang;Ren, Shuhua
非小细胞肺癌（Non-small cell lung cancer，NSCLC）是世界范围内癌症相关死亡的主要原因，其中肺腺癌是NSCLC的主要类型。MicroRNA是一种小的、非编码的单链RNA，可调节人类癌症中的基因表达。本研究的目的是探讨miR-142- 3 p在NSCLC中的潜在分子机制。RT-qPCR检测肺腺癌组织和细胞中miR-142- 3 p的表达。分别用CCK-8法、划痕法、transwell法和流式细胞术检测A549和HCC 827细胞的增殖、迁移、侵袭和凋亡。利用targetscanHuman7.2软件预测miR-142- 3 p的靶点，并通过双荧光素酶报告基因分析进行验证。采用RT-qPCR和western blot检测NR 2F 6、MMP 2、MMP 9和caspase-3的表达。结果显示，miR-142- 3 p在肿瘤组织和细胞中的表达明显降低。miR-142- 3 p过表达抑制细胞增殖、迁移、侵袭，促进细胞凋亡，而敲低miR-142- 3 p则相反。此外，NR 2F 6被鉴定为miR-142- 3 p的直接靶点，其与miR-142- 3 p表达呈负相关。miR-142- 3 p过表达抑制NR 2F 6、MMP 2和MMP 9的表达，但提高caspase-3的表达，而miR-142- 3 p敲低则得到相反的表达结果。抑制MMP 2和MMP 9活性可抑制细胞侵袭。综上所述，这些发现表明miR-142- 3 p通过靶向NR 2F 6抑制肺腺癌细胞增殖、迁移和侵袭，并促进细胞凋亡，提示miR-142- 3 p可能是肺腺癌治疗的新靶点。
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide and lung adenocarcinoma is its main type. MicroRNAs are small, non-coding and single-strand RNAs that regulate gene expression in human cancers. The aim of our study is to investigate the underlying molecular mechanism of miR-142-3p in NSCLC. The expression of miR-142-3p in lung adenocarcinoma tissues and cells was detected by RT-qPCR. Next, cell proliferation, migration, invasion and apoptosis were examined by CCK-8, scratch assay, transwell assay and flow cytometry in A549 and HCC827 cells, respectively. Then, the target of miR-142-3p was predicted by targetscanHuman 7.2 and confirmed using dual-luciferase reporter assay. Additionally, RT-qPCR and western blot were used to detect the expression of NR2F6, MMP2, MMP9 and caspase-3. The results showed that miR-142-3p expression was significantly decreased in tumor tissues and cells. Overexpression of miR-142-3p inhibited the proliferation, migration, invasion and promoted cell apoptosis in vitro, while knockdown of miR-142-3p had reversed function. Furthermore, NR2F6 was identified as a direct target of miR-142-3p, which was negatively correlated with miR-142-3p expression. Finally, miR-142-3p overexpression suppressed the expression of NR2F6, MMP2 and MMP9, but improved caspase-3 expression, while miR-142-3p knockdown got the opposite expression results. Suppressing MMP2 and MMP9 activities inhibited cell invasion. In summary, these findings indicated that miR-142-3p inhibits lung adenocarcinoma cell proliferation, migration and invasion, and enhances cell apoptosis by targeting NR2F6, suggesting that miR-142-3p may be a novel therapeutic target for lung adenocarcinoma treatment.