Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer.
Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer.
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miR-486-5p 的下调通过靶向肺癌中的促肿瘤 ARHGAP5 促进肿瘤进展和转移
作者：
我们之前已经证明miR-486-5p是肺癌中下调最严重的microRNAs之一。本研究旨在探讨miR-486-5p在非小细胞肺癌(NSCLC)进展和转移中的作用。应用定量逆转录聚合酶链式反应技术检测76例冷冻和33例福尔马林固定的非小细胞肺癌石蜡包埋组织中miR-486-5p的表达情况，以确定其临床病理意义。然后，我们进行了miR-486-5p的功能分析，以确定其在癌细胞体外迁移和侵袭以及体内转移中的潜在作用。我们还研究了miR-486-5p在肺肿瘤发生中的靶基因。MiR-486-5p在肺癌组织中的表达水平显著低于相应的正常肺组织(P<；0.0001)，并与非小细胞肺癌的分期(P=0.0001)和淋巴结转移(P=0.0019)有关。强制表达miR-486-5p可通过抑制细胞增殖抑制NSCLC细胞的体外迁移、侵袭和转移。此外，miR-486-5p在癌细胞中的异位表达降低了ARHGAP5的表达水平，而miR-486-5p的沉默则增加了它的表达。荧光素酶分析表明miR-486-5p能直接与ARHGAP5的3‘-非翻译区结合。肺癌组织中miR486-5p和ArHGAP5的表达水平呈负相关(P=0.0156)。与miR-486-5p过表达相似，ARHGAP5的低表达显著抑制了肺癌细胞的迁移和侵袭。MIR-486-5p可能通过靶向ARHGAP5发挥肿瘤抑制作用，参与非小细胞肺癌的进展和转移。MIR-486-5P将为该病提供潜在的诊断和治疗靶点。
We have previously shown that miR-486-5p is one of the most downregulated micro RNAs in lung cancer. The objective of the study was to investigate the role of miR-486-5p in the progression and metastasis of non-small-cell lung cancer (NSCLC). We evaluated miR-486-5p expression status on 76 frozen and 33 formalin-fixed paraffin-embedded tissues of NSCLC by quantitative reverse transcriptase PCR to determine its clinicopathologic significance. We then performed function analysis of miR-486-5p to determine its potential roles on cancer cell migration and invasion in vitro and metastasis in vivo. We also investigated the target genes of miR-486-5p in lung tumorigenesis. miR-486-5p expression level was significantly lower in lung tumors compared with their corresponding normal tissues (P< 0.0001), and associated with stage (P= 0.0001) and lymph node metastasis of NSCLC (P= 0.0019). Forced expression of miR-486-5p inhibited NSCLC cell migration and invasion in vitro and metastasis in mice by inhibiting cell proliferation. Furthermore, ectopic expression of miR-486-5p in cancer cells reduced ARHGAP5 expression level, whereas miR-486-5p silencing increased its expression. Luciferase assay demonstrated that miR-486-5p could directly bind to the 3′-untranslated region of ARHGAP5. The expression level of miR-486-5p was inversely correlated with that of ARHGAP5 in lung tumor tissues (P= 0.0156). Reduced expression of ARHGAP5 considerably inhibited lung cancer cell migration and invasion, resembling that of miR-486-5p overexpression. miR-486-5p may act as a tumor-suppressor contributing to the progression and metastasis of NSCLC by targeting ARHGAP5. miR-486-5p would provide potential diagnostic and therapeutic targets for the disease.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
11.5
作者：
Oh, Hue-Kian;Tan, Angie Lay-Keng;Tan, Patrick
通讯作者：
Tan, Patrick
影响因子：
9.8
作者：
Bansal, Ajay;Lee, I. H.;Christenson, L. K.
通讯作者：
Christenson, L. K.
DOI：
10.1186/bcr2352
发表时间：
2009
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Heckman-Stoddard BM;Vargo-Gogola T;McHenry PR;Jiang V;Herrick MP;Hilsenbeck SG;Settleman J;Rosen JM
通讯作者：
Rosen JM
DOI：
10.1083/jcb.119.3.493
发表时间：
1992-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gavrieli Y;Sherman Y;Ben-Sasson SA
通讯作者：
Ben-Sasson SA