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微小 RNA-381 作为一个预后因子,通过靶向 LRH-1 抑制非小细胞肺癌的迁移和侵袭。

MicroRNA-381 serves as a prognostic factor and inhibits migration and invasion in non-small cell lung cancer by targeting LRH-1.

机构信息

Department of Oncology, Cangnan Hospital Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Tumor Department of Hematology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

出版信息

Oncol Rep. 2017 Nov;38(5):3071-3077. doi: 10.3892/or.2017.5956. Epub 2017 Sep 14.

DOI:10.3892/or.2017.5956
PMID:29048619
Abstract

Accumulating evidence has demonstrated that aberrant miRNAs were involved in carcinogenesis and tumor progression by regulating oncogenes or tumor suppressor expression. Dysregulation of miR-381 has been reported in different tumors. However, the clinical roles and underlying mechanism in non-small cell lung cancer (NSCLC) remains to be elucidated. We found the expression of miR-381 was significantly downregulated in both NSCLC tissues and cell lines. Clinical analysis revealed the reduced miR-381 was obviously associated with advanced TNM stage and lymph node metastasis. Moreover, we disclosed that miR-381 was a novel independent prognostic marker for predicting 5-year survival of NSCLC patients. The ectopic overexpression of miR-381 inhibited cell migration and invasion in vitro and in vivo. Notably, miR-381 could modulate LRH-1 by directly binding to its 3'-UTR. In clinical samples of NSCLC, miR-381 inversely correlated with LRH-1 expression, which performed positive roles in NSCLC migration and invasion. Alteration of LRH-1 expression at least partially abolished the migration and invasion of miR-381 on NSCLC cells. Here, we identified LRH-1 as a functional target of miR-381 in NSCLC. In conclusion, our data indicated that miR-381 inhibited migration and invasion of NSCLC by targeting LRH-1, and may represent a novel potential therapeutic target and prognostic marker for NSCLC.

摘要

越来越多的证据表明,异常表达的 microRNA(miRNA)通过调节癌基因或肿瘤抑制基因的表达,参与了癌症的发生和肿瘤的进展。miR-381 在不同的肿瘤中失调已有报道。然而,其在非小细胞肺癌(NSCLC)中的临床作用和潜在机制仍有待阐明。我们发现 miR-381 在 NSCLC 组织和细胞系中的表达均显著下调。临床分析表明,miR-381 的减少与晚期 TNM 分期和淋巴结转移明显相关。此外,我们揭示了 miR-381 是预测 NSCLC 患者 5 年生存率的一个新的独立预后标志物。miR-381 的异位过表达抑制了 NSCLC 细胞的迁移和侵袭。值得注意的是,miR-381 可以通过直接与其 3'UTR 结合来调节 LRH-1。在 NSCLC 的临床样本中,miR-381 与 LRH-1 的表达呈负相关,LRH-1 在 NSCLC 的迁移和侵袭中发挥着积极的作用。LRH-1 表达的改变至少部分消除了 miR-381 对 NSCLC 细胞迁移和侵袭的影响。在这里,我们确定 LRH-1 是 miR-381 在 NSCLC 中的功能性靶标。总之,我们的数据表明,miR-381 通过靶向 LRH-1 抑制 NSCLC 的迁移和侵袭,可能代表 NSCLC 的一个新的潜在治疗靶点和预后标志物。

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