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miR-140-5p 靶向调控单核细胞向巨噬细胞分化相关基因(MMD)抑制非小细胞肺癌肿瘤生长。

Monocyte to macrophage differentiation-associated (MMD) targeted by miR-140-5p regulates tumor growth in non-small cell lung cancer.

机构信息

Department of Biomedical Engineering, Fourth Military Medical University, Xi'an 710032, China.

Department of Hepatic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Biochem Biophys Res Commun. 2014 Jul 18;450(1):844-50. doi: 10.1016/j.bbrc.2014.06.075. Epub 2014 Jun 24.

Abstract

Monocyte to macrophage differentiation-associated (MMD) is identified in macrophages as a gene associated with the differentiation from monocytes to macrophages. Recent microarray analysis for non-small cell lung cancer (NSCLC) suggests that MMD is an important signature associated with relapse and survival among patients with NSCLC. Therefore, we speculate that MMD likely plays a role in lung cancer. In this study, we found that the protein level of MMD was increased in lung cancer compared to benign lung tissues, and knockdown of MMD inhibited the growth of A549 and Lewis lung cancer cells (LLC) in vitro and in vivo. Integrated analysis demonstrated that MMD was a direct functional target of miR-140-5p. Furthermore, we found that miR-140-5p/MMD axis could affect the cell proliferation of lung cancer cells by regulating Erk signaling. Together, our results highlight the significance of miR-140-5p/MMD axis in lung cancer, and miR-140-5p/MMD axis could serve as new molecular targets for the therapy against lung cancer.

摘要

单核细胞向巨噬细胞分化相关(MMD)在巨噬细胞中被鉴定为与单核细胞向巨噬细胞分化相关的基因。最近对非小细胞肺癌(NSCLC)的微阵列分析表明,MMD 是与 NSCLC 患者复发和生存相关的重要特征。因此,我们推测 MMD 可能在肺癌中发挥作用。在这项研究中,我们发现与良性肺组织相比,肺癌组织中 MMD 的蛋白水平升高,并且敲低 MMD 可抑制 A549 和 Lewis 肺癌细胞(LLC)的体外和体内生长。综合分析表明,MMD 是 miR-140-5p 的直接功能靶标。此外,我们发现 miR-140-5p/MMD 轴可以通过调节 Erk 信号通路来影响肺癌细胞的增殖。总之,我们的研究结果强调了 miR-140-5p/MMD 轴在肺癌中的重要性,并且 miR-140-5p/MMD 轴可能成为治疗肺癌的新分子靶点。

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