Department of Respiratory Medicine, Dongying People's Hospital, Dongying, China. yanhouling@.163.com.
Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6845-6852. doi: 10.26355/eurrev_201810_16153.
To explore the role of microRNA-24 (miR-24) in the proliferation and apoptosis of lung carcinoma, and to investigate its underlying mechanism.
The expression level of miR-24 in 50 pairs of lung carcinoma tissues and para-cancerous tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The relationship between miR-24 expression and pathological indicators of lung carcinoma was analyzed. Meanwhile, the corresponding plasmids of miR-24 were constructed. The viability, proliferation, apoptosis and cell cycle of lung carcinoma cells after transfection with miR-24 plasmids were detected by cell counting kit-8 (CCK-8), colony formation assay, and flow cytometry, respectively. The binding condition of miR-24 and MAPK7 was predicted by bioinformatics and verified by Luciferase reporter gene assay. The regulatory effect of miR-24 on MAPK7 in lung carcinoma cells was further detected.
MiR-24 was significantly overexpressed in lung carcinoma tissues than that of para-cancerous tissues. Compared with lung carcinoma patients with Grade I-II and tumor size smaller than 3 cm, upregulated miR-24 expression was observed in those with Grade III-IV and tumor size larger than 3 cm. The overall survival (OS) of patients with higher miR-24 expression was remarkably shorter than those with lower expression. Results of clinical data analysis suggested that miR-24 expression was correlated with tumor size and tumor node metastasis (TNM), whereas not correlated with age, gender and lymph node metastasis. In vitro experiments demonstrated that miR-24 overexpression promoted the viability, proliferation and cell cycle of lung carcinoma cells, whereas inhibited cell apoptosis. Furthermore, luciferase reporter gene assay indicated that miR-24 could bind to MAPK7. Meanwhile, overexpressed miR-24 resulted in decreased mRNA and protein levels of MAPK7. In addition, decreased apoptosis and increased cell cycle induced by miR-24 overexpression could be partially reversed by MAPK7 overexpression.
We found that miR-24 promoted lung carcinoma development by increasing cell proliferation and inhibiting cell apoptosis via targeting MAPK7.
探讨 microRNA-24（miR-24）在肺癌增殖和凋亡中的作用及其机制。
采用实时定量聚合酶链反应（qRT-PCR）检测 50 对肺癌组织及癌旁组织中 miR-24 的表达水平，分析 miR-24 表达与肺癌病理指标的关系。同时构建 miR-24 相应质粒，通过细胞计数试剂盒-8（CCK-8）、集落形成实验和流式细胞术分别检测转染 miR-24 质粒后肺癌细胞的活力、增殖、凋亡和细胞周期。通过生物信息学预测 miR-24 与 MAPK7 的结合情况，并通过荧光素酶报告基因实验验证。进一步检测 miR-24 对肺癌细胞中 MAPK7 的调控作用。
miR-24 在肺癌组织中表达明显高于癌旁组织。与Ⅰ-Ⅱ级、肿瘤直径小于 3cm 的肺癌患者相比，Ⅲ-Ⅳ级、肿瘤直径大于 3cm 的肺癌患者中 miR-24 表达上调。miR-24 高表达患者的总生存期（OS）明显短于低表达患者。临床数据分析结果表明，miR-24 表达与肿瘤大小和肿瘤淋巴结转移（TNM）有关，与年龄、性别和淋巴结转移无关。体外实验表明，miR-24 过表达促进肺癌细胞的活力、增殖和细胞周期，而抑制细胞凋亡。此外，荧光素酶报告基因实验表明，miR-24 可以与 MAPK7 结合。同时，miR-24 过表达导致 MAPK7 的 mRNA 和蛋白水平降低。此外，miR-24 过表达诱导的凋亡减少和细胞周期增加可部分被 MAPK7 过表达逆转。
我们发现 miR-24 通过靶向 MAPK7 增加细胞增殖和抑制细胞凋亡促进肺癌的发展。
