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鸟氨酸转氨酶通过上调 miR-21 促进非小细胞肺癌的增殖和转移。

Ornithine aminotransferase promoted the proliferation and metastasis of non-small cell lung cancer via upregulation of miR-21.

机构信息

Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Department of Emergency, The First Affiliated Hospital of Xi'an Medical University, Xi'an, China.

出版信息

J Cell Physiol. 2019 Aug;234(8):12828-12838. doi: 10.1002/jcp.27939. Epub 2018 Dec 13.

Abstract

The incidence and mortality of lung cancer ranked the first among all types of cancer in China, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for 85% of all lung cancers. Given that the survival rate of patients with advanced NSCLC is still poor nowadays, identification of novel therapeutic targets and the development of effective therapies are desired for the treatment of NSCLC in clinics. In this study, we reported the upregulation of ornithine aminotransferase (OAT) in NSCLC cells and clinical tumor samples as well as its association with the advanced TNM stage, metastasis, and poor tumor differentiation of lung cancer. Using different NSCLC cell lines, we demonstrated that OAT promoted the proliferation, invasion, and migration, inhibited the apoptosis, and altered cell cycle of NSCLC cells; besides, the involvement of OAT-miR-21-glycogen synthase kinase-3β signaling in the functional role of OAT in NSCLC was also revealed. Importantly, in the absence of OAT, the growth and metastasis of tumor lung cancer xenograft was significantly suppressed in the nude mice. Based on our findings, OAT may be a potential novel biomarker for the diagnosis and therapeutic outcome monitoring of NSCLC. Inhibition of OAT may also represent a new therapeutic strategy of NSCLC.

摘要

在中国,肺癌的发病率和死亡率在所有癌症类型中均位居首位,而非小细胞肺癌(NSCLC)是最常见的肺癌类型,占所有肺癌的 85%。鉴于目前晚期 NSCLC 患者的生存率仍然较差,因此临床上需要鉴定新的治疗靶点并开发有效的治疗方法。在这项研究中,我们报告了 NSCLC 细胞和临床肿瘤样本中鸟氨酸转氨酶(OAT)的上调及其与肺癌的晚期 TNM 分期、转移和肿瘤分化不良的相关性。通过使用不同的 NSCLC 细胞系,我们证明了 OAT 可促进 NSCLC 细胞的增殖、侵袭和迁移,抑制凋亡并改变细胞周期;此外,OAT-miR-21-糖原合成酶激酶-3β信号通路参与了 OAT 在 NSCLC 中的功能作用。重要的是,在缺乏 OAT 的情况下,裸鼠中肿瘤肺转移的生长和转移明显受到抑制。基于我们的研究结果,OAT 可能是 NSCLC 诊断和治疗效果监测的潜在新型生物标志物。OAT 的抑制也可能代表 NSCLC 的一种新的治疗策略。

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