Department of Oncology, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, Fujian, China.
Infectious Disease Department, The People's Hospital of Ningde City, Ningde, Fujian, China.
Cancer Biomark. 2017 Dec 6;20(4):539-546. doi: 10.3233/CBM-170350.
MicroRNAs (miRNAs) emerge as important regulators involved in malignant progression in some tumors. MiR-181a has been found to function as a tumor suppressor in some tumors including non-small cell lung cancer (NSCLC). However, the functional role of miR-181a in NSCLC still needed to be investigated.
The expression of miR-181a were determined by qRT-PCR, the association between miR-181a and clinicopathological data were performed by chi-square test and survival analysis were evaluated by Kaplan-Meier curve and log rank test. Cell proliferation and invasion were assessed by CCK8, cell colony formation and transwell assays. Luciferase reporter assay demonstrated that CDK1 was a target of miR-181a. Western blot assay detected the relative protein expression.
In the study, our results showed that miR-181a was significantly down-regulated in non-small cell lung cancer (NSCLC) tissues and cell lines. MiR-181 expression levels were significantly associated with histological grade, N status and TNM stage in the patients and lower miR-181a predicted a poor prognosis in NSCLC patients. Furthermore, upregulation of miR-181a significantly suppressed the NSCLC cell proliferation, colony formation, and cell invasion capacities. Moreover, upregulation of miR-181a inhibited CyclinB1 and CyclinD1 expression in NSCLC cells. Luciferase activity assay results demonstrated CDK1 was a direct target of miR-181a and miR-181a inhibited cell proliferation by regulating the mRNA and protein levels of CDK1 in NSCLC cells.
These data suggested that miR-181a plays a tumor suppressor and may be a potential therapeutic target for NSCLC patients.
微小 RNA（miRNAs）作为一些肿瘤中恶性进展的重要调节因子而出现。miR-181a 在一些肿瘤中作为肿瘤抑制因子发挥作用，包括非小细胞肺癌（NSCLC）。然而，miR-181a 在 NSCLC 中的功能作用仍需进一步研究。
通过 qRT-PCR 确定 miR-181a 的表达，通过卡方检验和生存分析评估 miR-181a 与临床病理数据的相关性，通过 Kaplan-Meier 曲线和对数秩检验评估生存分析。通过 CCK8、细胞集落形成和 Transwell 测定评估细胞增殖和侵袭。荧光素酶报告测定显示 CDK1 是 miR-181a 的靶标。Western blot 测定检测相对蛋白表达。
在本研究中，我们的结果表明 miR-181a 在非小细胞肺癌（NSCLC）组织和细胞系中显著下调。miR-181 表达水平与患者的组织学分级、N 状态和 TNM 分期显著相关，miR-181a 低表达预示 NSCLC 患者预后不良。此外，miR-181a 的上调显著抑制 NSCLC 细胞的增殖、集落形成和细胞侵袭能力。此外，miR-181a 的上调抑制了 NSCLC 细胞中 CyclinB1 和 CyclinD1 的表达。荧光素酶活性测定结果表明 CDK1 是 miR-181a 的直接靶标，miR-181a 通过调节 NSCLC 细胞中 CDK1 的 mRNA 和蛋白水平抑制细胞增殖。
这些数据表明 miR-181a 发挥肿瘤抑制作用，可能是 NSCLC 患者的潜在治疗靶点。
