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微小 RNA-449a 在非小细胞肺癌中下调,并通过靶向 c-Met 抑制迁移和侵袭。

MicroRNA-449a is downregulated in non-small cell lung cancer and inhibits migration and invasion by targeting c-Met.

机构信息

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.

出版信息

PLoS One. 2013 May 29;8(5):e64759. doi: 10.1371/journal.pone.0064759. Print 2013.

Abstract

MicroRNA-449a is expressed at a low level in several tumors and cancer cell lines, and induces G1 arrest, apoptosis, and senescence. To identify the function of miR-449a in non-small cell lung cancer (NSCLC), we discussed the potential relevance of miR-449a to clinicopathological characteristics and prognosis in NSCLC. We also investigated the impact of miR-449a on migration and invasion in NSCLC cells. The expression of miR-449a in NSCLC tissues and cell lines was detected using RT-qPCR. In vitro, gain-of-function, loss-of-function experiments, and fluorescence assays were performed to identify the potential target of miR-449a and the function of miR-449a in NSCLC cells. MiR-449a was downregulated in both NSCLC tissues and cell lines. Moreover, a low expression level of miR-449a appeared to be correlated with lymph node metastasis and poor survival. In vitro, miR-449 regulated cell migration and invasion in NSCLC cells as a potential tumor suppressor, at least in part by targeting c-Met. Furthermore, reciprocal expression of miR-449a and c-Met was shown in NSCLC tissue samples. This study indicates that miR-449a might be associated with NSCLC progression, and suggests a crucial role for miR-449a in NSCLC.

摘要

miR-449a 在多种肿瘤和癌细胞系中低表达,并诱导 G1 期阻滞、凋亡和衰老。为了确定 miR-449a 在非小细胞肺癌(NSCLC)中的功能,我们探讨了 miR-449a 与 NSCLC 临床病理特征和预后的潜在相关性。我们还研究了 miR-449a 对 NSCLC 细胞迁移和侵袭的影响。采用 RT-qPCR 检测 NSCLC 组织和细胞系中 miR-449a 的表达。在体外,通过功能获得和功能丧失实验以及荧光测定法,鉴定 miR-449a 的潜在靶标及其在 NSCLC 细胞中的功能。miR-449a 在 NSCLC 组织和细胞系中均下调。此外,miR-449a 的低表达水平似乎与淋巴结转移和不良预后相关。在体外,miR-449a 作为一种潜在的肿瘤抑制因子,调节 NSCLC 细胞的迁移和侵袭,至少部分是通过靶向 c-Met 实现的。此外,在 NSCLC 组织样本中观察到 miR-449a 和 c-Met 的表达呈反向关系。本研究表明,miR-449a 可能与 NSCLC 的进展有关,并提示 miR-449a 在 NSCLC 中具有重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfe0/3667122/59ee5e8488bb/pone.0064759.g001.jpg

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