Methylation of an intronic region regulates miR-199a in testicular tumor malignancy.
Methylation of an intronic region regulates miR-199a in testicular tumor malignancy.
复制标题
DOI：
10.1038/onc.2011.60
复制
发表时间：
2011-08-04
期刊：
影响因子：
8
通讯作者：
Chan, W-Y
中科院分区：
文献类型：
--
作者：
Cheung, H-H;Davis, A. J.;Lee, T-L;Pang, A. L.;Nagrani, S.;Rennert, O. M.;Chan, W-Y
在睾丸癌细胞系NT2中，我们先前证明了差异甲基化区域位于内含子或基因间区域，并假设这些区域可能调节非编码rna。3种微rna和3种小核仁rna存在差异甲基化；其中一个miR-199a与胃癌和卵巢癌的进展和预后相关。在本报告中，我们通过睾丸组织的表观基因组分析证实，miR-199a转录为动力蛋白3的反义位点（染色体1q24.3），该区域的高甲基化与miR-199a-5p/3p抑制和肿瘤恶性相关。在睾丸癌细胞中重新表达miR-199a可抑制细胞生长、肿瘤迁移、侵袭和转移。miR-199a-5p是源自miR-199a的两种成熟miRNA之一，与肿瘤恶性相关。我们进一步确定了胚胎癌抗原podocalyxin-like protein 1 (PODXL)，一种在侵袭性肿瘤中表达的抗粘附蛋白，作为miR-199a-5p的靶标。我们证明了PODXL在恶性睾丸肿瘤中过表达，并且PODXL的细胞缺失导致肿瘤侵袭受到抑制。PODXL与miR-199a-5p表达呈负相关，表明PODXL是介导miR199a-5p作用的下游效应因子。该报告确定了DNA甲基化、miR-199a失调和PODXL是肿瘤恶性的关键因素。
In the testicular cancer cell line, NT2, we previously demonstrated that differentially methylated regions were located in introns or intergenic regions, and postulated these might regulate non-coding RNAs. Three micro-RNAs and three small nucleolar RNAs were differentially methylated; one, miR-199a, was associated with the progression and prognosis of gastric and ovarian cancers. In this report we document, by epigenomic profiling of testicular tissue, that miR-199a is transcribed as antisense of dynamin 3 (chromosome 1q24.3), and hypermethylation of this region is correlated with miR-199a-5p/3p repression and tumor malignancy. Re-expression of miR-199a in testicular cancer cells led to suppression of cell growth, cancer migration, invasion and metastasis. The miR-199a-5p, one of two mature miRNA species derived from miR-199a, is associated with tumor malignancy. We further identified the embryonal carcinoma antigen podocalyxin-like protein 1 (PODXL), an anti-adhesive protein expressed in aggressive tumors, as a target of miR-199a-5p. We demonstrated PODXL is overexpressed in malignant testicular tumor, and cellular depletion of PODXL resulted in suppression of cancer invasion. The inverse relationship between PODXL and miR-199a-5p expression suggests PODXL is a downstream effector mediating the action of miR199a-5p. This report identifies DNA methylation, miR-199a dysregulation and PODXL as critical factors in tumor malignancy.
登录
查看更多内容
影响因子：
4.8
作者：
Kim, Seonhoe;Lee, Ui Jin;Choi, Young-Chul
通讯作者：
Choi, Young-Chul
影响因子：
11.5
作者：
Nam, Eun Ji;Yoon, Heejei;Kim, Sunghoon
通讯作者：
Kim, Sunghoon
影响因子：
3.6
作者：
Pang, Alan Lap-Yin;Peacock, Stephanie;Chan, Wai-Yee
通讯作者：
Chan, Wai-Yee
影响因子：
--
作者：
Cheung, Hoi-Hung;Lee, Tin-Lap;Rennert, Owen M.;Chan, Wai-Yee
通讯作者：
Chan, Wai-Yee
影响因子：
8.8
作者：
通讯作者：
--