Blockade of miR-3614 maturation by IGF2BP3 increases TRIM25 expression and promotes breast cancer cell proliferation
Blockade of miR-3614 maturation by IGF2BP3 increases TRIM25 expression and promotes breast cancer cell proliferation
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DOI：
10.1016/j.ebiom.2018.12.061
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发表时间：
2019-03-01
期刊：
影响因子：
11.1
通讯作者：
Huang, Chen
中科院分区：
文献类型：
--
作者：
Wang, Zhenzhen;Tong, Dongdong;Huang, Chen
背景：RNA结合蛋白（RBP）和microRNA（miRNAs）在基因表达调控中的相互作用是一个复杂的过程。方法：采用qRT-PCR、Western blot和免疫组化方法检测TRIM 25、IGF 2BP 3、pri-miR-3614和miR-3614 - 3 p在乳腺癌组织、非肿瘤组织和乳腺癌细胞株中的表达水平。使用荧光素酶活化测定、RNA免疫沉淀（RIP）和生物素下拉测定验证miR-3614- 3 p和IGF 2BP 3与TRIM 25 RNA的结合。通过体外和体内实验研究IGF 2BP 3-miR-3614- 3 p-TRIM 25轴在乳腺癌细胞增殖中的作用及相关机制，发现基因内miRNA-3614 - 3 p通过与TRIM 25的3 '-非翻译区（UTR）结合，抑制其宿主基因TRIM 25的表达。有趣的是，IGF 2BP 3可以竞争性地占据该结合位点并抑制miRNA-3614成熟，从而保护TRIM 25 mRNA免受miR-3614介导的降解。miR-3614- 3 p的过表达通过下调TRIM 25显著抑制乳腺癌细胞生长。此外，IGF 2BP 3的沉默降低了TRIM 25的表达，抑制了细胞增殖，并表现出与miR-3614- 3 p过表达的协同效应。解释：总的来说，这些结果表明，通过IGF 2BP 3和miR-3614- 3 p之间的相互作用控制TRIM 25 RNA代表了乳腺癌细胞增殖的机制。陕西省科研与共享平台建设项目、陕西省颅面精准医学研究重点实验室开放项目、国家博士后科学基金、国家自然科学基金。(c)2018由Elsevier B出版。V.这是CC BY-NC-ND许可下的开放获取文章（http：//creativecommons. org/许可证/by-nc-nd/4.0/）。
Background: The cross-talk between RNA binding proteins (RBPs) and microRNAs (miRNAs) in the regulation of gene expression is a complex process. Here, we describe a new mode of regulation of TRIM25 expression mediated by an antagonistic interplay between IGF2BP3 and miR-3614-3p.Methods: The expression level of TRIM25, IGF2BP3, pri-miR-3614 and miR-3614-3p in breast cancer (BC) tissues, non-tumor tissues and BC cell lines were detected by qRT-PCR, Western blot and Immunohistochemistry (IHC). Binding ofmiR-3614-3p and IGF2BP3 to TRIM25 RNAwas verified using luciferase activation assays, RNA immunoprecipitation (RIP) and biotin pull-down assays. In vitro and in vivo loss-and gain-of-function studies were performed to reveal the effects and relatedmechanismof IGF2BP3-miR-3614-3p-TRIM25 axis in in breast cancer cells proliferation.Findings: Wefound that an intragenicmiRNA-3614-3p inhibits the expression of its host gene TRIM25 by binding to its 3'-untranslated region (UTR). Interestingly, IGF2BP3 can competitively occupy this binding site and inhibit miRNA-3614 maturation, thereby protecting TRIM25 mRNA frommiR-3614-mediated degradation. The overexpression of miR-3614-3p dramatically inhibited breast cancer cell growth through the downregulation of TRIM25. Furthermore, the silencing of IGF2BP3 reduced TRIM25 expression, suppressed cell proliferation, and exhibited a synergistic effect with miR-3614-3p overexpression.Interpretation: Collectively, these results demonstrate that control of TRIM25 RNA by an interplay between IGF2BP3 and miR-3614-3p represents a mechanism for breast cancer cell proliferation.Fund: The scientific research and sharing platform construction project of Shaanxi Province, Opening Project of Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, China Postdoctoral Science Foundation and The National Natural Science Foundation of China. (c) 2018 Published by Elsevier B. V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).