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微小RNA-661通过直接靶向RUNX3促进非小细胞肺癌进展。

MicroRNA-661 promotes non-small cell lung cancer progression by directly targeting RUNX3.

作者信息

Wang Yu, Li Yuqiang, Wu Bin, Shi Ce, Li Chen

机构信息

Department of Molecular Detection, Center for Clinical Biological Samples, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, Liaoning, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):2113-2120. doi: 10.3892/mmr.2017.6827. Epub 2017 Jun 21.

Abstract

Lung cancer is the primary cause of cancer‑associated mortality in men and women worldwide. Increasing evidence indicates that abnormal microRNA (miRNA) expression contributes to the carcinogenesis and progression of multiple human cancers, including non‑small cell lung cancer (NSCLC). Therefore, miRNAs exhibit the potential to act as biomarkers for the diagnosis, treatment and prognosis of human malignancies. miRNA‑661 (miR‑661) has previously been demonstrated to be important in the development of various human cancer types. However, the expression levels, functions and underlying mechanisms of miR‑661 in NSCLC remain to be elucidated. The present study demonstrated that miR‑661 was upregulated in NSCLC tissues and cell lines. In addition, miR‑661 expression levels were significantly correlated with differentiation and tumor stage lymph node metastasis of NSCLC patients. Functional experiments demonstrated that miR-661 downregulation inhibited NSCLC cell proliferation and invasion in vitro. Furthermore, runt‑related transcription factor 3 (RUNX3) was identified as a direct target of miR‑661 in NSCLC. RUNX3 was expressed at a low level in NSCLC tissues and was negatively correlated with the miR‑661 expression level. Further experiments revealed that RUNX3 knockdown significantly rescued the effects of miR‑661 underexpression on NSCLC cell proliferation and invasion. In conclusion, the present findings indicated a role for miR‑661 as an oncogene in NSCLC via direct targeting of RUNX3, thus suggesting that miR‑661 may be used to develop novel therapies for NSCLC patients.

摘要

肺癌是全球男性和女性癌症相关死亡的主要原因。越来越多的证据表明,异常的微小RNA(miRNA)表达促进了包括非小细胞肺癌(NSCLC)在内的多种人类癌症的发生和发展。因此,miRNA具有作为人类恶性肿瘤诊断、治疗和预后生物标志物的潜力。miRNA-661(miR-661)先前已被证明在多种人类癌症类型的发展中起重要作用。然而,miR-661在NSCLC中的表达水平、功能及潜在机制仍有待阐明。本研究表明,miR-661在NSCLC组织和细胞系中上调。此外,miR-661表达水平与NSCLC患者的分化程度和肿瘤分期淋巴结转移显著相关。功能实验表明,miR-661下调可抑制NSCLC细胞在体外的增殖和侵袭。此外, runt相关转录因子3(RUNX3)被确定为NSCLC中miR-661的直接靶点。RUNX3在NSCLC组织中低表达,且与miR-661表达水平呈负相关。进一步实验表明,RUNX3敲低可显著挽救miR-661低表达对NSCLC细胞增殖和侵袭的影响。总之,本研究结果表明miR-661通过直接靶向RUNX3在NSCLC中作为癌基因发挥作用,从而提示miR-661可用于开发针对NSCLC患者的新疗法。

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