Jiang Feng, Yu Qiuhua, Chu Ying, Zhu Xiaobo, Lu Wenbin, Liu Qian, Wang Qiang
Department of Cardiothoracic Surgery, Wujin People's Hospital of Changzhou, Changzhou, Jiangsu 213017, P.R. China.
Central Laboratory, Wujin People's Hospital of Changzhou, Changzhou, Jiangsu 213017, P.R. China.
Int J Oncol. 2019 Jan;54(1):128-138. doi: 10.3892/ijo.2018.4610. Epub 2018 Oct 29.
MicroRNAs (miRNAs or miRs) have recently emerged as key regulators of various types of cancer, including non‑small cell lung cancer (NSCLC). The disrupted expression of miRNAs is associated with tumorigenesis and metastasis; however, the underlying mechanisms remain unclear. In this study, we demonstrate that miR‑98‑5p is downregulated in NSCLC and that miR‑98‑5p deficiency is associated with an advanced clinical stage and metastasis. A dual‑luciferase reporter assay was performed to confirm that transforming growth factor beta receptor 1 (TGFBR1), a key stimulator of tumor proliferation and metastasis, was a direct target of miR‑98‑5p. miR‑98‑5p overexpression resulted in the downregulation of TGFBR1 and the suppression of the viability, proliferation, migration and invasion of A549 and H1299 cells. Furthermore, miR‑98‑5p was demonstrated to be an efficient suppressor of tumor growth in an A549 subcutaneous xenograft tumor mouse model. Finally, miR‑98‑5p overexpression exerted a significant anti‑metastatic effect in a mouse model of pulmonary metastasis. On the whole, the results of the present study suggest that miR‑98‑5p/TGFBR1 may serve as promising targets for NSCLC therapy.
微小RNA(miRNA或miR)最近已成为包括非小细胞肺癌(NSCLC)在内的各种癌症的关键调节因子。miRNA表达的紊乱与肿瘤发生和转移有关;然而,其潜在机制仍不清楚。在本研究中,我们证明miR-98-5p在NSCLC中表达下调,且miR-98-5p缺乏与晚期临床分期和转移相关。进行双荧光素酶报告基因检测以确认转化生长因子β受体1(TGFBR1),肿瘤增殖和转移的关键刺激因子,是miR-98-5p的直接靶标。miR-98-5p过表达导致TGFBR1下调,并抑制A549和H1299细胞的活力、增殖、迁移和侵袭。此外,在A549皮下异种移植肿瘤小鼠模型中,miR-98-5p被证明是肿瘤生长的有效抑制剂。最后,miR-98-5p过表达在肺转移小鼠模型中发挥了显著的抗转移作用。总体而言,本研究结果表明miR-98-5p/TGFBR1可能成为NSCLC治疗的有希望的靶点。