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Identification of microRNA signature in the progression of gestational trophoblastic disease

机译:鉴定妊娠滋养细胞疾病进展中的microRNA标记

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Gestational trophoblastic disease (GTD) encompasses a range of trophoblast-derived disorders. The most common type of GTD is hydatidiform mole (HM). Some of HMs can further develop into malignant gestational trophoblastic neoplasia (GTN). Aberrant expression of microRNA (miRNA) is widely reported to be involved in the initiation and progression of cancers. MiRNA expression profile also has been proved to be the useful signature for diagnosis, staging, prognosis, and response to chemotherapy. Till now, the profile of miRNA in the progression of GTD has not been determined. In this study, a total of 34 GTN and 60 complete HMs (CHM) trophoblastic tissues were collected. By miRNA array screening and qRT-PCR validating, six miRNAs, including miR-370-3p, -371a-5p, -518a-3p, -519d-3p, -520a-3p, and -934, were identified to be differentially expressed in GTN vs. CHM. Functional analyses further proved that miR-371a-5p and miR-518a-3p promoted proliferation, migration, and invasion of choriocarcinoma cells. Moreover, we demonstrated that miR-371a-5p was negatively related to protein levels of its predictive target genes BCCIP, SOX2, and BNIP3L, while miR-518a-3p was negatively related to MST1 and EFNA4. For the first time, we proved that miR-371a-5p and miR-518a-3p directly targeted to 3′-UTR regions of BCCIP and MST1, respectively. Additionally, we found that miR-371a-5p and miR-518a-3p regulated diverse pathways related to tumorigenesis and metastasis in choriocarcinoma cells. The results presented here may offer new clues to the progression of GTD and may provide diagnostic biomarkers for GTN.
机译:妊娠滋养细胞疾病(GTD)涵盖了一系列滋养细胞疾病。 GTD的最常见类型是葡萄胎(HM)。一些重症肌无力可进一步发展为恶性妊娠滋养细胞赘生物(GTN)。广泛报道了microRNA(miRNA)的异常表达与癌症的发生和发展有关。 MiRNA表达谱也已被证明是诊断,分期,预后和对化疗反应的有用标志。迄今为止,尚未确定miRNA在GTD进程中的概况。在这项研究中,总共收集了34个GTN和60个完整的HMs(CHM)滋养细胞组织。通过miRNA阵列筛选和qRT-PCR验证,鉴定出包括miR-370-3p,-371a-5p,-518a-3p,-519d-3p,-520a-3p和-934在内的六个miRNA差异表达。在GTN与CHM中。功能分析进一步证明,miR-371a-5p和miR-518a-3p可以促进绒癌组织的增殖,迁移和侵袭。此外,我们证明了miR-371a-5p与其预测目标基因BCCIP,SOX2和BNIP3L的蛋白质水平呈负相关,而miR-518a-3p与MST1和EFNA4呈负相关。我们首次证明miR-371a-5p和miR-518a-3p分别直接靶向BCCIP和MST1的3'-UTR区。此外,我们发现miR-371a-5p和miR-518a-3p调节了绒癌组织中与肿瘤发生和转移相关的多种途径。此处提供的结果可能为GTD的进展提供新的线索,并可能提供GTN的诊断生物标志物。

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