MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis.
MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis.
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DOI：
10.18632/oncotarget.11722
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发表时间：
2016-10-18
期刊：
影响因子：
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通讯作者：
Rao L
中科院分区：
文献类型：
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作者：
Su Y;Xiong J;Hu J;Wei X;Zhang X;Rao L
microRNA（miRNAs）是一类在肿瘤发生和发展中起重要作用的非编码小RNA分子。先前的研究表明，MicroRNA-140- 5 p（miR-140- 5 p）在几种癌症中异常表达。然而，其在宫颈癌（CC）中的功能和可能的机制仍不清楚。本研究数据挖掘结果显示，miR-140- 5 p在CC标本中表达下调，且miR-140- 5 p表达下调与CC预后不良相关。这些观察结果促使我们进一步研究miR-140- 5 p在人类CC发病机制中的作用和机制。我们发现miR-140- 5 p的过表达/抑制显著降低/增加CC细胞的体外增殖、迁移和侵袭。同时，体内实验结果表明，过表达miR-140- 5 p能显著抑制裸鼠肿瘤的生长和转移。此外，胰岛素样生长因子2 mRNA结合蛋白1（IGF 2BP 1）被鉴定为miR-140- 5 p的直接靶点，并且功能获得和功能丧失测定均揭示IGF 2BP 1也是miR-140- 5 p的功能靶点。综上所述，我们的研究结果表明，一种新的miR-140- 5 p-IGF 2BP 1调控电路CC发病机制，和miR-140- 5 p可能是一个潜在的目标CC治疗。
MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play important roles in carcinogenesis and tumor progression. Previous studies have revealed that MicroRNA-140-5p (miR-140-5p) was abnormally expressed in several cancers. However, its function and possible mechanism in cervical cancer (CC) remains unknown. In this study, the data mining results showed that miR-140-5p was down-regulated in CC specimens and the down-regulation of miR-140-5p was associated with CC poor prognosis. These observations prompted us to further investigate the roles and mechanisms of miR-140-5p in human CC pathogenesis. We found that the over-expression/inhibition of miR-140-5p significantly decreased/increased cell proliferation, migration, and invasion in CC cells in vitro. Meanwhile, the results from in vivo assays showed that the over-expression of miR-140-5p induced significantly suppression of tumor growth and metastasis in nude mice. Furthermore, Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was identified as a direct target of miR-140-5p, and both gain-of-function and loss-of-function assays revealed that IGF2BP1 is also a functional target of miR-140-5p. Taken together, our findings suggested a novel miR-140-5p-IGF2BP1 regulatory circuit for CC pathogenesis, and miR-140-5p may be a potential target for CC therapy.