IGF2BP3 enhances the mRNA stability of E2F3 by interacting with LINC00958 to promote endometrial carcinoma progression.
IGF2BP3 enhances the mRNA stability of E2F3 by interacting with LINC00958 to promote endometrial carcinoma progression.
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IGF2BP3通过与LINC00958相互作用增强E2F3 mRNA稳定性促进子宫内膜癌进展
DOI：
10.1038/s41420-022-01045-x
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发表时间：
2022-06-08
影响因子：
7
通讯作者：
Ma, Xiaoxin
中科院分区：
文献类型：
--
作者：
Wang, Cuicui;Kong, Fanfei;Ma, Jian;Miao, Jianing;Su, Peng;Yang, Hui;Li, Qing;Ma, Xiaoxin
长链非编码RNA（longnoncodingRNAs，lncRNA）在肿瘤的多种病理过程中起着重要的调控作用。然而，子宫内膜癌（EC）中lncRNA调控的确切分子机制仍不清楚。本研究的目的是阐明LINC 00958调节IGF 2BP 3（一种参与mRNA稳定性的RNA结合蛋白）功能的机制及其在EC中的临床意义。首先，我们研究了IGF 2BP 3在EC中的临床作用，并证明了其预后价值。功能丧失和功能获得研究表明，IGF 2BP 3促进EC细胞增殖、迁移和侵袭。然后，我们进行了RNA免疫沉淀测序（RIP-seq）分析、RNA下拉和免疫荧光-RNA荧光原位杂交，鉴定了EC细胞质中与IGF 2BP 3相互作用的LINC 00958。拯救实验表明，LINC 00958的敲低部分抵消了IGF 2BP 3介导的EC细胞进展。然后通过RNA测序筛选出IGF 2BP 3和LINC 00958的下游基因。结果表明，IGF 2BP 3通过与LINC 00958相互作用上调E2 F3表达。此外，RNA稳定性测定表明，沉默LINC 00958部分挽救了IGF 2BP 3介导的对E2 F3 mRNA稳定性的促进作用。总的来说，这项研究表明，LINC 00958，作为一种癌基因，协助IGF 2BP 3稳定E2 F3 mRNA，并最终促进EC进展，为EC患者提供了一个有希望的治疗靶点。
Long noncoding RNAs (lncRNAs) play important regulatory roles in a variety of pathological processes involving cancer. However, the exact molecular mechanisms of lncRNA regulation in endometrial carcinoma (EC) remain poorly defined. The aim of this study was to illustrate the mechanism of LINC00958 in regulating the function of IGF2BP3, an RNA binding protein involved in mRNA stability, and their clinical implications in EC. First, we investigated the clinical role of IGF2BP3 in EC and demonstrated its prognostic value. Loss-of-function and gain-of-function studies showed that IGF2BP3 promoted EC cell proliferation, migration and invasion. Then, we carried out RNA immunoprecipitation sequencing (RIP-seq) analysis, RNA pulldown and immunofluorescence-RNA fluorescence in situ hybridization to identify LINC00958 that interacted with IGF2BP3 in the cytoplasm of EC cells. Rescue experiments indicated that knockdown of LINC00958 partially offset the EC cell progression mediated by IGF2BP3. After that, RNA sequencing was used to screen out the downstream genes of IGF2BP3 and LINC00958. The results revealed that IGF2BP3 upregulated E2F3 expression by interacting with LINC00958. Furthermore, RNA stability assays demonstrated that silencing LINC00958 partially rescued the IGF2BP3-mediated promoting effect on the mRNA stability of E2F3. Collectively, this study suggests that LINC00958, as an oncogene, assists IGF2BP3 in stabilizing E2F3 mRNA and ultimately promotes EC progression, providing a promising therapeutic target for patients with EC.
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