MicroRNA-1253 suppresses cell proliferation and invasion of non-small-cell lung carcinoma by targeting WNT5A.
MicroRNA-1253 suppresses cell proliferation and invasion of non-small-cell lung carcinoma by targeting WNT5A.
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DOI：
10.1038/s41419-017-0218-x
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发表时间：
2018-02-07
影响因子：
9
通讯作者：
Sun G
中科院分区：
文献类型：
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作者：
Liu M;Zhang Y;Zhang J;Cai H;Zhang C;Yang Z;Niu Y;Wang H;Wei X;Wang W;Gao P;Li H;Zhang J;Sun G
MicroRNAs(MiRNA)是一类调节靶基因表达的非编码小RNA分子。MiRNA的失调参与了肿瘤的发生和发展。在这项研究中，我们发现microRNA-1253(miR-1253)在非小细胞肺癌(NSCLC)组织中显著下调，并与晚期临床分期、淋巴转移和低生存率相关。MiR-1253表达增强可显著抑制NSCLC细胞的增殖、迁移和侵袭。生物信息学分析表明，miR-1253直接靶向Wnt5A(长的异构体)，并通过双荧光素酶报告基因分析证实了这一点。Wnt5A(Long)过表达和基因敲除分别减弱和抑制miR-1253对NSCLC细胞生长和转移的抑制作用。与体外结果一致的是，皮下肿瘤和转移性NSCLC小鼠模型表明，miR-1253在体内对NSCLC具有有效的抑制作用。综上所述，我们的研究结果表明miR-1253通过靶向Wnt5A(长异构体)抑制NSCLC细胞的增殖和转移，为miR-1253成为NSCLC潜在的治疗靶点提供了新的证据。
MicroRNAs (miRNA) are a class of small, noncoding RNA molecules that regulate the expression of target genes. miRNA dysregulation is involved in carcinogenesis and tumor progression. In this study, we identified microRNA-1253 (miR-1253) as being significantly down-regulated in non-small-cell lung carcinoma (NSCLC) tissues and associated with advanced clinical stage, lymph node metastasis, and poor survival. The enhanced expression of miR-1253 significantly inhibited the proliferation, migration, and invasion of NSCLC cells in vitro. Bioinformatics analyses showed that miR-1253 directly targeted WNT5A (long isoform), which was confirmed using the dual-luciferase reporter assay. The inhibitory effects of miR-1253 on the growth and metastasis of NSCLC cells were attenuated and phenocopied by WNT5A (long) overexpression and knockdown, respectively. Consistent with the in vitro results, subcutaneous tumor and metastatic NSCLC mouse models showed that miR-1253 functions as a potent suppressor of NSCLC in vivo. Taken together, our findings indicated that miR-1253 inhibited the proliferation and metastasis of NSCLC cells by targeting WNT5A (long isoform) and provided new evidence of miR-1253 as a potential therapeutic target in NSCLC.
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