microRNA-93 promotes cell proliferation via targeting of PTEN in Osteosarcoma cells.
microRNA-93 promotes cell proliferation via targeting of PTEN in Osteosarcoma cells.
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DOI：
10.1186/s13046-015-0192-z
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发表时间：
2015-08-05
期刊：
影响因子：
--
通讯作者：
Tsumura H
中科院分区：
文献类型：
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作者：
Kawano M;Tanaka K;Itonaga I;Ikeda S;Iwasaki T;Tsumura H
microRNA （miRNA）的异常表达在骨肉瘤（OS）的发病机制中起重要作用。最近的研究表明，miRNA表达失调与几种类型的癌症（包括OS）的肿瘤发生增加和预后不良有关。本研究的目的是研究参与OS发展的相关microrna。为了探索OS中可能的致癌因素，我们使用了一种基于微阵列的方法来分析5种OS细胞系和人间充质干细胞（hMSCs）中mirna及其靶mrna的表达变化。与hMSCs相比，所有测试的OS细胞中miR-93的表达均显著上调，而磷酸酶和紧张素同源物（PTEN）的表达均显著下调。将anti-miR-93转染到OS细胞系后，PTEN的表达显著增加，提示PTEN可能是miR-93在ES细胞中的靶标。已知与PTEN呈负相关的磷酸化Akt蛋白在anti- mir -93转染的细胞中表达显著下调。此外，转染anti-miR-93可抑制胚胎干细胞的增殖和细胞周期进程。此外，在这些细胞中下调miR-93在体内显著抑制肿瘤生长。miR-93的异位表达降低了PTEN蛋白水平。此外，miR-93增加了OS细胞的增殖并减少了凋亡，而在这些细胞中沉默miR-93则抑制了这种致癌过程。综上所述，miR-93可以通过抑制PTEN在癌变中发挥关键作用，并可能作为治疗OS的治疗靶点。
Aberrant microRNA (miRNA) expression plays an essential role in osteosarcoma (OS) pathogenesis. Recent studies have shown that dysregulation of miRNA expression is associated with increased tumorigenesis and poor prognosis in several types of cancers, including OS. The aim of this study was to investigate the relevant microRNAs involved in the development of OS. To explore possible oncogenic factors in OS, we used a microarray-based approach to profile changes in the expression of miRNAs and their target mRNAs in five OS cell lines and human mesenchymal stem cells (hMSCs). An miRNA, miR-93, was significantly up-regulated, whereas phosphatase and tensin homologue (PTEN) expression was significantly down-regulated in all tested OS cells, when compared with hMSCs. When anti-miR-93 was transfected into OS cell lines, PTEN expression was greatly increased, suggesting that PTEN might be a target of miR-93 in ES cells. The expression of phosphorylated Akt protein, which is known to be inversely correlated with that of PTEN, was significantly down-regulated in anti-miR-93-transfected cells. Furthermore, transfection of anti-miR-93 inhibited the proliferation and cell cycle progression of ES cells. In addition, the down-regulation of miR-93 in these cells significantly suppressed tumor growth in vivo. Ectopic expression of miR-93 decreased PTEN protein levels. Furthermore, miR-93 increased proliferation and decreased apoptosis in OS cells, whereas its silencing in these cells inhibited such carcinogenic processes. Taking these observations together, miR-93 can be seen to play a critical role in carcinogenesis through suppression of PTEN, and may serve as a therapeutic target for the treatment of OS.