MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma.
MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma.
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DOI：
10.1186/s12958-018-0364-8
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发表时间：
2018-05-11
期刊：
影响因子：
--
通讯作者：
Styer AK
中科院分区：
文献类型：
--
作者：
Cardozo ER;Foster R;Karmon AE;Lee AE;Gatune LW;Rueda BR;Styer AK
MicroRNA (MiR) 可能通过改变参与细胞增殖和 ECM 形成的基因表达来促进肌瘤的发展，并且有证据支持 MicroRNA (MiR) 21a-5p 在肌瘤中的异常表达。本研究的目的是探讨 MiR 21a-5p 过表达在平滑肌瘤（肌瘤）病理学中的功能意义。使用源自患者匹配样本的永生化肌瘤和子宫肌细胞系的基础科学实验设计。通过慢病毒载体感染，在永生化肌瘤和患者匹配的子宫肌细胞系中实现了 MiR-21a-5p 的稳定过表达。主要结果指标是 MiR-21-5p 过表达、靶基因和蛋白质表达、胶原蛋白 (COL1A1) 产生、细胞增殖、细胞迁移以及肌瘤和子宫肌层永生化细胞系的细胞周期阶段。慢病毒感染后，miR-21a-5p 在肌瘤细胞系和子宫肌层细胞系中过表达至相似水平。 miR-21 表达增加导致肌瘤细胞和子宫肌层细胞中 TGF-β3 基因和蛋白表达增加。在肌瘤细胞和子宫肌层细胞中均观察到 ECM 基因纤连蛋白、胶原蛋白 1A1、CTGF、Versacan 和 DPT 表达的变化。肌瘤细胞和子宫肌层细胞中基质金属蛋白酶 (MMP) 相关基因（包括 MMP 2、MMP 9、MMP 11 和 Serpine 1）也发生了变化。与子宫肌层细胞相比，miR-21 上调导致肌瘤细胞增殖和迁移增加。 MiR-21a-5p 过表达导致肌瘤细胞和子宫肌层细胞中 ECM 介质表达的变化，并增加肌瘤细胞中的细胞增殖。这些发现表明 MiR-21a-5p 在子宫肌瘤的发展中具有潜在的功能作用，值得进一步研究。本文的在线版本 (10.1186/s12958-018-0364-8) 包含补充材料，可供授权用户使用。
MicroRNAs (MiR) may promote fibroid development via altered expression of genes involved in cell proliferation and ECM formation, and evidence supports aberrant expression of MicroRNA (MiR) 21a-5p in fibroids. The purpose of this study was to investigate the functional significance of MiR 21a-5p overexpression in the pathobiology of leiomyomata (fibroids). A basic science experimental design using immortalized fibroid and myometrial cell lines derived from patient-matched specimens was used. Stable overexpression of MiR-21a-5p in an immortalized fibroid and patient matched myometrial cell line was achieved through lentiviral vector infection. Main outcome measures were MiR-21-5p overexpression, target gene and protein expression, collagen (COL1A1) production, cell proliferation, cell migration, and cell cycle stages of fibroid and myometrial immortalized cell lines. MiR-21a-5p was overexpressed to similar levels in fibroid and myometrial cell lines after lentiviral infection. Increased expression of miR-21 resulted in increased gene and protein expression of TGF-β3 in both fibroid and myometrial cells. Changes in expression of the ECM genes Fibronectin, Collagen 1A1, CTGF, Versican and DPT were seen in both fibroid and myometrial cells. Changes were also seen in Matrix Metalloproteinase (MMP) related genes including MMP 2, MMP 9, MMP 11 and Serpine 1 in both fibroid and myometrial cells. MiR-21 upregulation resulted in increased proliferation and migration in fibroid cells compared to myometrial cells. MiR-21a-5p overexpression results in changes in the expression of ECM mediators in both fibroid and myometrial cells, and increased cell proliferation in fibroid cells. These finding suggest a potential functional role of MiR-21a-5p in the development of uterine fibroids and warrant further investigation. The online version of this article (10.1186/s12958-018-0364-8) contains supplementary material, which is available to authorized users.
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影响因子：
4
作者：
Noetel A;Kwiecinski M;Elfimova N;Huang J;Odenthal M
通讯作者：
Odenthal M
影响因子：
3.9
作者：
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影响因子：
9.8
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Kwon OS;Kim KT;Lee E;Kim M;Choi SH;Li H;Fornace AJ Jr;Cho JH;Lee YS;Lee JS;Lee YJ;Cha HJ
通讯作者：
Cha HJ
影响因子：
3.9
作者：
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通讯作者：
Kolb, M.