MicroRNA-548j functions as a metastasis promoter in human breast cancer by targeting Tensin1.
MicroRNA-548j functions as a metastasis promoter in human breast cancer by targeting Tensin1.
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MicroRNA-548j 通过靶向 Tensin1 作为人类乳腺癌的转移促进剂。
DOI：
10.1016/j.molonc.2016.02.002
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Liu Zhihua
中科院分区：
文献类型：
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作者：
Zhan Yun;Liang Xiaoshuan;Li Lin;Wang Baona;Ding Fang;Li Yi;Wang Xiang;Zhan Qimin;Liu Zhihua
微小RNA（miRNA）是参与重要生物过程的单链非编码小RNA分子。虽然许多miRNAs在乳腺癌转移中的功能已经被确定，但其他miRNAs的作用仍有待于表征。为了鉴定参与转移的另外的miRNA，我们通过将Lenti-miR™病毒文库转导到MCF-7细胞中来进行遗传筛选。使用transwell侵袭测定，我们鉴定了人miR-548 j作为侵袭诱导miRNA。乳腺癌细胞系中miR-548 j表达的内源性水平显示与侵袭性相关。此外，miR-548 j在体外和体内显示出刺激乳腺癌细胞的侵袭和转移，但对增殖没有影响。接下来，通过一系列的体外和体内实验，我们发现Tensin 1是miR-548 j的直接功能靶点。miR-548 j和Tensin 1均能调节Cdc 42的活化以调节细胞侵袭，siCdc 42或Cdc 42选择性抑制剂ML 141可抑制miR-548 j介导的细胞侵袭途径。此外，使用两组临床乳腺癌样品观察到miR-548 j、Tensin 1、转移和存活之间的强相关性。我们的研究结果表明，miR-548 j作为一种转移促进miRNA，通过靶向Tensin 1和激活Cdc 42来调节乳腺癌细胞的侵袭和转移，这表明在乳腺癌中具有潜在的治疗应用。
MicroRNAs (miRNAs) are single-stranded, small non-coding RNA molecules that participate in important biological processes. Although the functions of many miRNAs in breast cancer metastasis have been established, the role of others remains to be characterized. To identify additional miRNAs involved in metastasis, we performed a genetic screen by transducing a Lenti-miR™ virus library into MCF-7 cells. Using transwell invasion assays we identified human miR-548j as an invasion-inducing miRNA. The endogenous levels of miR-548j expression in breast cancer cell lines were shown to correlate with invasiveness. Moreover, miR-548j was shown to stimulate breast cancer cell invasion and metastasisin vitroandin vivo, but had no effect on proliferation. Next, using a series ofin vitroandin vivoexperiments, we found that Tensin1 served as a direct and functional target of miR-548j. Both miR-548j and Tensin1 modulated the activation of Cdc42 to regulate cell invasion and siCdc42 or the selective Cdc42 inhibitor ML141 suppressed the pathway of miR-548j-mediated cell invasion. Furthermore, a strong correlation between miR-548j, Tensin1, metastasis and survival was observed using two sets of clinical breast cancer samples. Our findings demonstrate that miR-548j functions as a metastasis-promoting miRNA to regulate breast cancer cell invasion and metastasis by targeting Tensin1 and activating Cdc42, suggesting a potential therapeutic application in breast cancer.