Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, China.
Department of pathology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, China.
PLoS Genet. 2018 Dec 17;14(12):e1007790. doi: 10.1371/journal.pgen.1007790. eCollection 2018 Dec.
Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was determined. Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. We demonstrated that miR-3607-3p was downregulated in NSCLC tissues and that miR-3607-3p might act as an independent predictor for overall survival in NSCLC. Moreover, serum miR-3607-3p may be a novel and stable marker for NSCLC. We found that overexpression of miR-3607-3p inhibited cell proliferation, colony formation, migration and invasion, and hampered the cell cycle of NSCLC cell lines in vitro. Our results suggested that miR-3607-3p directly targets TGFBR1 and CCNE2. In accordance with in vitro studies, we confirmed that miR-3607-3p functions as a potent suppressor miRNA of NSCLC. We showed that miR-3607-3p agomir could reduce tumor growth and inhibit TGFBR1 and CCNE2 protein expression. Taken together, our findings indicate that miR-3607-3p can inhibit NSCLC cell growth and metastasis by targeting TGFBR1 and CCNE2 protein expression, and provide new evidence of miR-3607-3p as a potential non-invasive biomarker and therapeutic target for NSCLC.
越来越多的证据表明，miRNA 可以作为各种癌症有前途的诊断和/或预后标志物。在这项研究中，我们鉴定了一种新型 miRNA，miR-3607-3p，及其在非小细胞肺癌（NSCLC）中的靶标。测量了 miR-3607-3p 的表达，并确定了其与患者预后的相关性。在 NSCLC 细胞、异种移植和转移模型中外源表达，以评估 miR-3607-3p 对 NSCLC 细胞增殖和迁移的影响。荧光素酶测定和 Western blot 用于验证通过微阵列分析和计算机辅助算法初步筛选后的潜在靶标。我们证明 miR-3607-3p 在 NSCLC 组织中下调，并且 miR-3607-3p 可能是 NSCLC 总生存的独立预测因子。此外，血清 miR-3607-3p 可能是 NSCLC 的一种新型和稳定的标志物。我们发现 miR-3607-3p 的过表达抑制了 NSCLC 细胞系的体外细胞增殖、集落形成、迁移和侵袭，并阻碍了细胞周期。我们的结果表明，miR-3607-3p 可以直接靶向 TGFBR1 和 CCNE2。与体外研究一致，我们证实 miR-3607-3p 作为 NSCLC 的有效抑制性 miRNA 发挥作用。我们表明 miR-3607-3p 激动剂可以减少肿瘤生长并抑制 TGFBR1 和 CCNE2 蛋白表达。总之，我们的研究结果表明，miR-3607-3p 通过靶向 TGFBR1 和 CCNE2 蛋白表达抑制 NSCLC 细胞生长和转移，并为 miR-3607-3p 作为 NSCLC 潜在的非侵入性生物标志物和治疗靶点提供了新的证据。
