Epigenetic Regulation of miR-129-2 Leads to Overexpression of PDGFRa and FoxP1 in Glioma Cells.
Epigenetic Regulation of miR-129-2 Leads to Overexpression of PDGFRa and FoxP1 in Glioma Cells.
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miR-129-2 的表观遗传调控导致胶质瘤细胞中 PDGFRa 和 FoxP1 的过度表达。
DOI：
10.7314/apjcp.2015.16.14.6129
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Li, Ming
中科院分区：
文献类型：
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作者：
Tian, Xiang-Yang;Zhang, Ling;Sun, Lai-Guang;Li, Ming
miR-129-2在多种癌症中经常下调。然而，它是如何在癌症中消失的仍不清楚。在这里，我们研究了miR-129-2在胶质母细胞瘤（GBM）中的表达谱和潜在的生物学功能，胶质母细胞瘤是成人中最常见和致命的脑肿瘤。我们发现miR-129-2在GBM患者标本和培养细胞系中丢失。组蛋白去乙酰化酶抑制剂（trichostatin a）可恢复miR-129-2的表达，但DNA甲基化抑制剂（5-Aza-2'-脱氧胞苷）不能恢复miR-129-2的表达，两种药物联合治疗效果更显著。此外，miR-129-2的强制表达抑制了GBMs中PDGFRa和Foxp1等主要致癌基因的表达。同样，miR-129-2的表达在体外显著抑制GBM细胞的增殖。这些结果表明，miR-129-2在GBM中受表观遗传调控，并作为肿瘤抑制基因发挥作用，提示其可能作为GBM治疗的潜在治疗靶点。
miR-129-2 is frequently downregulated in multiple cancers. However, how it is silenced in cancers remains unclear. Here we investigated the expression profile and potential biological function of miR-129-2 in glioblastoma (GBM), the most common and lethal form of brain tumors in adults. We showed that miR-129-2 is lost in GBM patient specimens and cultured cell lines. miR-129-2 expression could be restored upon treatment with a histone deadetylase inhibitor (trichostatin A) but not a DNA methylation inhibitor (5-Aza-2'-deoxycytidine), and more profound effect was observed with the treatment of these two drugs in combination. Furthermore, forced expression of miR-129-2 repressed the expression of major oncogenic genes such as PDGFRa and Foxp1 in GBMs. Consistently, expression of miR-129-2 significantly inhibits GBM cell proliferation in vitro. These results reveal that miR-129-2 is epigenetically regulated and functions as a tumor suppressor gene in GBMs, suggesting it may serve as a potential therapeutic target for GBM treatment.
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影响因子：
11.2
作者：
Huang YW;Liu JC;Deatherage DE;Luo J;Mutch DG;Goodfellow PJ;Miller DS;Huang TH
通讯作者：
Huang TH
影响因子：
4
作者：
Fesler A;Zhai H;Ju J
通讯作者：
Ju J
影响因子：
11.2
作者：
Gomez GG;Volinia S;Croce CM;Zanca C;Li M;Emnett R;Gutmann DH;Brennan CW;Furnari FB;Cavenee WK
通讯作者：
Cavenee WK
影响因子：
21.3
作者：
Ma, Li;Young, Jennifer;Prabhala, Harsha;Pan, Elizabeth;Mestdagh, Pieter;Muth, Daniel;Teruya-Feldstein, Julie;Reinhardt, Ferenc;Onder, Tamer T.;Valastyan, Scott;Westermann, Frank;Speleman, Frank;Vandesompele, Jo;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
影响因子：
9
作者：
通讯作者：
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