Department of Thoracic Surgery, Peking Union Medical College Hospital (PUMCH), NO.1 Shuaifuyuan Road, Dongcheng District, Beijing 100730, China; Department of Thoracic Surgery, Peking Union Medical College, Chinese Academy of Medical Sciences, NO.1 Shuaifuyuan Road, Dongcheng District, Beijing 100730, China.
Department of Thoracic Surgery, Peking Union Medical College Hospital (PUMCH), NO.1 Shuaifuyuan Road, Dongcheng District, Beijing 100730, China; Department of Thoracic Surgery, Peking Union Medical College, Chinese Academy of Medical Sciences, NO.1 Shuaifuyuan Road, Dongcheng District, Beijing 100730, China.
Gene. 2018 Oct 30;675:278-284. doi: 10.1016/j.gene.2018.06.062. Epub 2018 Jun 20.
Aberrantly microRNAs (miRs) expression is reported to be involved in tumorigenesis and development in non-small cell lung cancer (NSCLC). MiR-340 had been identified to be downregulated in NSCLC in the previous study. However, the underlying mechanisms of miR-340 involved in NSCLC progression still needed to be well known. In the present study, we confirmed that miR-340 expression was notably down-regulated in NSCLC tissues compared to matched adjacent noncancerous lung tissues by quantitative real time PCR (qRT-PCR) analyses. Lower miR-340 expression positively related to lymph node metastasis, larger tumor size, advanced TNM stage and poor prognosis of NSCLC patients. In vitro assays, we demonstrated that upregulation of miR-340 expression suppressed cell proliferation ability. Bioinformatics analysis and luciferase reporter assays revealed that miR-340 directly targeted the 3'-untranslated (3'UTR) region of CDK4 mRNA. Over-expression of miR-340 suppressed cell proliferation by regulating CDK4 expression in NSCLC cells. Additionally, we showed that increased miR-340 expression promoted the expression of cell proliferation related protein CDK6 expression, but decreasing the P15 and P21 expression. In vivo, we verified that miR-340 overexpression also inhibited tumor growth by regulating CDK4 expression. Therefore, these findings revealed miR-340 functions as a tumor suppressor in NSCLC cells and may provide a potential target of NSCLC treatment.
异常表达的 microRNAs（miRs）被报道与非小细胞肺癌（NSCLC）的发生和发展有关。先前的研究已经发现 miR-340 在 NSCLC 中下调。然而，miR-340 参与 NSCLC 进展的潜在机制仍需要进一步研究。在本研究中，我们通过定量实时 PCR（qRT-PCR）分析证实 miR-340 在 NSCLC 组织中的表达明显低于配对的相邻非癌性肺组织。较低的 miR-340 表达与淋巴结转移、肿瘤体积较大、TNM 分期较晚和 NSCLC 患者预后不良呈正相关。在体外实验中，我们证明上调 miR-340 的表达抑制了细胞增殖能力。生物信息学分析和荧光素酶报告实验表明，miR-340 直接靶向 CDK4 mRNA 的 3'-非翻译区（3'UTR）。在 NSCLC 细胞中，通过调节 CDK4 表达，过表达 miR-340 抑制细胞增殖。此外，我们还表明，miR-340 表达增加促进了细胞增殖相关蛋白 CDK6 的表达，同时降低了 P15 和 P21 的表达。在体内，我们验证了 miR-340 的过表达也通过调节 CDK4 表达抑制肿瘤生长。因此，这些发现表明 miR-340 在 NSCLC 细胞中作为一种肿瘤抑制因子发挥作用，可能为 NSCLC 的治疗提供一个潜在的靶点。
