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微小RNA-1976作为一种肿瘤抑制因子,通过直接靶向磷脂酶Cε1(PLCE1),在非小细胞肺癌中作为一种预后指标。

MicroRNA-1976 functions as a tumor suppressor and serves as a prognostic indicator in non-small cell lung cancer by directly targeting PLCE1.

作者信息

Chen Gang, Hu Jing, Huang Zhao, Yang Lijing, Chen Min

机构信息

Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.

Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.

出版信息

Biochem Biophys Res Commun. 2016 May 13;473(4):1144-1151. doi: 10.1016/j.bbrc.2016.04.030. Epub 2016 Apr 8.

Abstract

Lung cancer remains a leading cause of cancer-associated mortality worldwide and non-small lung cancer (NSCLC) is responsible for over 80% of lung cancer-related deaths. Identifying novel molecular biomarker that can inhibit the progression of lung cancer will facilitate the development of new treatment strategies. Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in NSCLC. Nevertheless, the role of PLCE1 in NSCLC tumorigenesis has not been elucidated. Herein, we demonstrated that miR-1976 is a tumor-suppressor miRNA in NSCLC progression. We found that expression of miR-1976 was decreased obviously in NSCLC tissues. Down-regulation of miR-1976 was associated with TNM stage and postoperative survival. Overexpression of miR-1976 inhibited the growth and metastasis of NSCLC cells. The PLCE1 was a direct target of miR-1976 and promoted the growth and metastasis of NSCLC cells. Further study showed that PLCE1 could reverse the inhibitory effect of miR-1976 on growth and metastasis of NSCLC cells. Taken together, our data highlight the pivotal role of miR-1976 in the progression of NSCLC. Thus, miR-1976 may be a potential prognostic marker and of treatment relevance for NSCLC progression intervention.

摘要

肺癌仍然是全球癌症相关死亡的主要原因,非小细胞肺癌(NSCLC)占肺癌相关死亡的80%以上。鉴定能够抑制肺癌进展的新型分子生物标志物将有助于新治疗策略的开发。磷脂酶Cε1(PLCE1)是NSCLC中的一个易感基因。然而,PLCE1在NSCLC肿瘤发生中的作用尚未阐明。在此,我们证明miR-1976是NSCLC进展中的一种肿瘤抑制性miRNA。我们发现miR-1976在NSCLC组织中的表达明显降低。miR-1976的下调与TNM分期和术后生存率相关。miR-1976的过表达抑制了NSCLC细胞的生长和转移。PLCE1是miR-1976的直接靶点,并促进NSCLC细胞的生长和转移。进一步研究表明,PLCE1可逆转miR-1976对NSCLC细胞生长和转移的抑制作用。综上所述,我们的数据突出了miR-1976在NSCLC进展中的关键作用。因此,miR-1976可能是一种潜在的预后标志物,对NSCLC进展干预具有治疗相关性。

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