Department II of Oncology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Eur Rev Med Pharmacol Sci. 2018 Sep;22(17):5531-5538. doi: 10.26355/eurrev_201809_15814.
To investigate the biological role of micro-ribonucleic acid (miR)-29a in non-small-cell lung cancer (NSCLC).
55 cases of NSCLC tissue specimens and paired normal lung tissue specimens collected in the Department II of Oncology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from July 2012 to April 2015 were randomly included. The fluorescent quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect the expression levels of miR-29a and metastasis suppressor 1 (MTSS1). Pearson correlation analysis was utilized to investigate the relationship between miR-29a expression and MTSS1 expression in NSCLC tissues, and the Kaplan-Meier survival curves were constructed to analyze the association of miR-29a expression with the survival time of NSCLC patients. A54 proliferation and invasion abilities were measured by means of plate clone formation assay, and transwell assay after the miR-29a was suppressed by miRNA inhibitor. Luciferase assay was used to detect the target gene of miR-29a.
In NSCLC tissues, the miR-29a expression level was higher than that in normal lung tissues (p<0.05), while the expression level of MTSS1 protein was remarkably lower than that in normal lung tissues (p<0.05). The median survival time of the patients was 15.1 months in high miR-29a expression group and 18.3 months in low miR-29a expression group (p<0.05). The miR-29a expression was negatively correlated with the expression level of MTSS1 protein in NSCLC tissues (r=-0.762, p<0.05). Luciferase results suggest that miR-29a binds to the promoter region of MTSS1 and inhibits its transcription level. The expression of MTSS1 protein was up-regulated notably after miR-29a knockdown by an inhibitor. It was revealed in the results of transwell assay and plate clone formation assay that the proliferative and invasive capacity of A549 cells was significantly decreased after knockdown of miR-29a.
The transcribed miR-29a down-regulates the protein level of MTSS1, suppressor of tumor proliferation and invasion, thereby promoting the proliferative and invasive capacity of NSCLC cells. Both miR-29a and MTSS1 are expected to become potential therapeutic targets for NSCLC.
探讨微小 RNA（miR）-29a 在非小细胞肺癌（NSCLC）中的生物学作用。
本研究纳入 2012 年 7 月至 2015 年 4 月广西中医药大学瑞康医院肿瘤科 II 区 55 例 NSCLC 组织标本和配对的正常肺组织标本。采用荧光定量聚合酶链反应、Western blot 及免疫组化法检测 miR-29a 和转移抑制因子 1（MTSS1）的表达水平。采用 Pearson 相关性分析探讨 NSCLC 组织中 miR-29a 表达与 MTSS1 表达的关系，采用 Kaplan-Meier 生存曲线分析 miR-29a 表达与 NSCLC 患者生存时间的关系。采用 miR-29a 抑制剂抑制 miR-29a 后，通过平板克隆形成试验和 Transwell 试验检测 A54 的增殖和侵袭能力。采用荧光素酶试验检测 miR-29a 的靶基因。
在 NSCLC 组织中，miR-29a 的表达水平高于正常肺组织（p<0.05），而 MTSS1 蛋白的表达水平明显低于正常肺组织（p<0.05）。高 miR-29a 表达组患者的中位生存时间为 15.1 个月，低 miR-29a 表达组为 18.3 个月（p<0.05）。miR-29a 的表达与 NSCLC 组织中 MTSS1 蛋白的表达水平呈负相关（r=-0.762，p<0.05）。荧光素酶结果表明，miR-29a 结合到 MTSS1 的启动子区域并抑制其转录水平。通过抑制剂敲低 miR-29a 后，MTSS1 蛋白的表达明显上调。Transwell 试验和平板克隆形成试验结果显示，敲低 miR-29a 后 A549 细胞的增殖和侵袭能力显著降低。
转录的 miR-29a 下调肿瘤增殖和侵袭抑制剂 MTSS1 的蛋白水平，从而促进 NSCLC 细胞的增殖和侵袭能力。miR-29a 和 MTSS1 均有望成为 NSCLC 的潜在治疗靶点。
