PDF(Pubmed)
Abstract：
Lung cancer is one of the deadliest cancers, in which non-small cell lung cancer (NSCLC) accounting for 85% and has a low survival rate of 5 years. Dysregulation of microRNAs (miRNAs) can participate in tumor regulation and many major diseases. In this study, we found that miR-199a-3p/5p were down-expressed in NSCLC tissue samples, cell lines, and the patient sample database. MiR-199a-3p/5p overexpression could significantly suppress cell proliferation, migration ability and promote apoptosis. Through software prediction, ras homolog enriched in brain (Rheb) was identified as a common target of miR-199a-3p and miR-199a-5p, which participated in regulating mTOR signaling pathway. The same effect of inhibiting NSCLC appeared after down-regulating the expression of Rheb. Furthermore, our findings revealed that miR-199a can significantly inhibit tumor growth and metastasis in vivo, which fully demonstrates that miR-199a plays a tumor suppressive role in NSCLC. In addition, miR-199a-3p/5p has been shown to enhance the sensitivity of gefitinib to EGFR-T790M in NSCLC. Collectively, these results prove that miR-199a-3p/5p can act as cancer suppressor genes to inhibit the mTOR signaling pathway by targeting Rheb, which in turn inhibits the regulatory process of NSCLC. Thus, to investigate the anti-cancer effect of pre-miR-199a/Rheb/mTOR axis in NSCLC, miR-199a-3p and miR-199a-5p have the potential to become an early diagnostic marker or therapeutic target for NSCLC.
摘要：
肺癌是最致命的癌症之一，其中非小细胞肺癌（NSCLC）占85%，5年生存率较低。microRNAs(miRNAs)的失调可参与肿瘤的调控和许多重大疾病的发生。在这项研究中,我们发现miR-199a-3p/5p在NSCLC组织样本中表达下调,细胞系,和病人样本数据库。MiR-199a-3p/5p过表达能显著抑制细胞增殖,迁移能力和促进细胞凋亡。通过软件预测,大脑中富集的ras同源物（Rheb）被鉴定为miR-199a-3p和miR-199a-5p的共同靶标，参与调节mTOR信号通路。在下调Rheb的表达后出现抑制NSCLC的相同效果。此外，我们的研究结果表明，miR-199a可以显著抑制体内肿瘤的生长和转移，这充分证明miR-199a在NSCLC中具有抑瘤作用。此外,miR-199a-3p/5p已显示在NSCLC中增强吉非替尼对EGFR-T790M的敏感性。总的来说，这些结果证明miR-199a-3p/5p可以作为抑癌基因通过靶向Rheb抑制mTOR信号通路,这反过来又抑制了NSCLC的调节过程。因此，探讨pre-miR-199a/Rheb/mTOR轴在非小细胞肺癌中的抗癌作用,miR-199a-3p和miR-199a-5p有可能成为NSCLC的早期诊断标志物或治疗靶标。
