Department of Thoracic Surgery, Yantaishan Hospital, Yantai, Shandong 264001, P.R. China.
Department of Radiotherapy, Yantaishan Hospital, Yantai, Shandong 264001, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3979-3986. doi: 10.3892/mmr.2017.8350. Epub 2017 Dec 27.
Lung cancer is one of the most common type of cancers and the leading cause of cancer‑related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for >80% of lung cancer cases. Emerging studies have suggested that microRNAs are dysregulated in NSCLC and serve important roles in NSCLC initiation and development. However, to the best of our knowledge, the expression, roles and molecular mechanism of microRNA‑454 (miR‑454) have not been investigated in NSCLC. In the present study, miR‑454 was demonstrated to be significantly downregulated in NSCLC tissues and cell lines, as assessed by western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Reduced miR‑454 expression was significantly correlated with aggressive clinicopathological features in NSCLC. In addition, upregulation of miR‑454 suppressed proliferation, migration and invasion NSCLC cells, as assessed by Cell Counting Kit‑8 and in vitro migration and invasion assays, respectively. Furthermore, bioinformatics analysis identified STAT3 as a direct target gene of miR‑454, and STAT3 knockdown was demonstrated to simulate the effects of miR‑454 overexpression in NSCLC. In conclusion, the present study provided convincing evidence that miR‑454 is downregulated in NSCLC, and regulates growth and metastasis by directly targeting STAT3, which suggests that miR‑454 may be an efficient therapeutic target for NSCLC.
肺癌是最常见的癌症类型之一,也是全球癌症相关死亡的主要原因。非小细胞肺癌(NSCLC)占肺癌病例的>80%。新兴研究表明,microRNAs 在 NSCLC 中失调,并在 NSCLC 的发生和发展中发挥重要作用。然而,据我们所知,microRNA-454(miR-454)在 NSCLC 中的表达、作用和分子机制尚未得到研究。在本研究中,通过 Western blot 分析和逆转录-定量聚合酶链反应评估,miR-454 在 NSCLC 组织和细胞系中明显下调。miR-454 表达降低与 NSCLC 侵袭性临床病理特征显著相关。此外,通过细胞计数试剂盒-8 和体外迁移和侵袭测定评估,miR-454 的上调抑制了 NSCLC 细胞的增殖、迁移和侵袭。此外,生物信息学分析鉴定 STAT3 为 miR-454 的直接靶基因,STAT3 敲低模拟了 miR-454 过表达在 NSCLC 中的作用。总之,本研究提供了令人信服的证据表明 miR-454 在 NSCLC 中下调,并通过直接靶向 STAT3 调节生长和转移,这表明 miR-454 可能是 NSCLC 的有效治疗靶点。