Genome-wide DNA methylation analysis reveals a potential mechanism for the pathogenesis and development of uterine leiomyomas.
Genome-wide DNA methylation analysis reveals a potential mechanism for the pathogenesis and development of uterine leiomyomas.
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DOI：
10.1371/journal.pone.0066632
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sugino N
中科院分区：
文献类型：
--
作者：
Maekawa R;Sato S;Yamagata Y;Asada H;Tamura I;Lee L;Okada M;Tamura H;Takaki E;Nakai A;Sugino N
子宫平滑肌瘤是女性最常见的良性肿瘤，其发病机制尚不清楚。由于后天因素，如肥胖，高血压和初潮早期子宫肌瘤的妇女在更大的风险，子宫肌瘤可能与表观遗传异常，由不利的环境暴露引起的。在子宫平滑肌瘤和有或无子宫平滑肌瘤的子宫肌层中研究了全基因组DNA甲基化和mRNA表达谱。DNA甲基化和mRNA表达谱在有和无平滑肌瘤的子宫肌层中非常相似，而在平滑肌瘤中则不同。我们确定了120个基因，其DNA甲基化和mRNA表达模式在平滑肌瘤和相邻的子宫肌层之间存在差异。甲基化和表达异常的基因与肿瘤过程有关，包括与转化相关的IRS1和胶原相关基因如COL4A1、COL4A2和COL6A3。我们还检测到22个雌激素受体（ER）α的靶基因，包括乳腺癌相关基因，在启动子中存在异常DNA甲基化，这表明ER α靶基因的异常表观遗传调控有助于对雌激素的异常反应。异常的DNA甲基化及其相关的转录异常与癌症过程相关，这可能是触发单个肿瘤干细胞转化的关键初始机制，最终将发展为单克隆平滑肌瘤肿瘤。ER α靶基因的异常表观遗传调控也可能导致对雌激素的异常反应，这与初潮后子宫平滑肌瘤的发展有关。
The pathogenesis of uterine leiomyomas, the most common benign tumor in women, remains unclear. Since acquired factors such as obesity, hypertension and early menarche place women at greater risk for uterine leiomyomas, uterine leiomyomas may be associated with epigenetic abnormalities that are caused by unfavorable environmental exposures. Profiles of genome-wide DNA methylation and mRNA expression were investigated in leiomyomas and in myometrium with and without leiomyomas. Profiles of DNA methylation and mRNA expression in the myometrium with and without leiomyomas were quite similar while those in leiomyomas were distinct. We identified 120 genes whose DNA methylation and mRNA expression patterns differed between leiomyomas and the adjacent myometrium. The biological relevance of the aberrantly methylated and expressed genes was cancer process, including IRS1 that is related to transformation, and collagen-related genes such as COL4A1, COL4A2 and COL6A3. We also detected 22 target genes of estrogen receptor (ER) alpha, including apoptosis-related genes, that have aberrant DNA methylation in the promoter, suggesting that the aberrant epigenetic regulation of ER alpha-target genes contributes to the aberrant response to estrogen. Aberrant DNA methylation and its related transcriptional aberration were associated with cancer processes, which may represent a critical initial mechanism that triggers transformation of a single tumor stem cell that will eventually develop into a monoclonal leiomyoma tumor. The aberrant epigenetic regulation of ER alpha-target genes also may contribute to the aberrant response to estrogen, which is involved in the development of uterine leiomyomas after menarche.
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DOI：
10.1158/1541-7786.mcr-11-0605
发表时间：
2012-04
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Greathouse KL;Bredfeldt T;Everitt JI;Lin K;Berry T;Kannan K;Mittelstadt ML;Ho SM;Walker CL
通讯作者：
Walker CL
影响因子：
3.7
作者：
Esposito DL;Aru F;Lattanzio R;Morgano A;Abbondanza M;Malekzadeh R;Bishehsari F;Valanzano R;Russo A;Piantelli M;Moschetta A;Lotti LV;Mariani-Costantini R
通讯作者：
Mariani-Costantini R
影响因子：
8
作者：
del Rincón, SV;Guo, Q;Miller, WH
通讯作者：
Miller, WH
影响因子：
1.8
作者：
Feng G;Du P;Krett NL;Tessel M;Rosen S;Kibbe WA;Lin SM
通讯作者：
Lin SM
影响因子：
14.9
作者：
Huang DW;Sherman BT;Tan Q;Kir J;Liu D;Bryant D;Guo Y;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA