[与卵巢癌发生和转移相关的miR-107、miR-130b、miR-203a、miR-1258基因的高甲基化]

[Hypermethylation of miR-107, miR-130b, miR-203a, miR-1258 Genes Associated with Ovarian Cancer Development and Metastasis].

作者信息

Loginov V I, Burdennyy A M, Filippova E A, Pronina I V, Kazubskaya T P, Kushlinsky D N, Ermilova V D, Rykov S V, Khodyrev D S, Braga E A

机构信息

Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia.

Research Center of Medical Genetics, Moscow, 115478 Russia.

出版信息

Mol Biol (Mosk). 2018 Sep-Oct;52(5):801-809. doi: 10.1134/S0026898418050105.

DOI:10.1134/S0026898418050105

PMID:30363055

Abstract

It is known that microRNAs (miRNAs) are able to dynamically regulate gene expression. At the same time, methylation can reduce expression of miRNA encoding genes and, therefore, reduce their inhibitory effects on mRNAs of target genes, including those of oncogenes, that promoting the development of tumors of different localization. The role of miRNA hypermethylation in the pathogenesis of ovarian cancer is not completely understood; so we conducted a search for new hypermethylated and potentially suppressor miRNA genes in ovarian tumors. Four new miRNA genes (MIR-107, MIR-130b, MIR-203a, MIR-1258) commonly hypermethylated (28-52%) in tumor tissues vs 4-7% in paired histologically normal tissues, p < 0.01, were identified in a representative set of 54 ovarian cancer samples using methylation-specific PCR. It was shown that hypermethylation of MIR-130b, MIR-203a, and MIR-1258 genes is significantly (p < 0.05) associated with metastasis of ovarian cancer. These results suggest the involvement of four miRNAs (miR-107, miR-130b, miR-203a, and miR-1258) and hypermethylation of their encoding genes in the pathogenesis of ovarian cancer.

摘要

已知微小RNA（miRNA）能够动态调节基因表达。同时，甲基化可降低miRNA编码基因的表达，从而降低其对靶基因mRNA（包括癌基因mRNA）的抑制作用，促进不同部位肿瘤的发展。miRNA高甲基化在卵巢癌发病机制中的作用尚未完全明确；因此，我们在卵巢肿瘤中寻找新的高甲基化且可能具有抑制作用的miRNA基因。使用甲基化特异性PCR，在一组54例卵巢癌样本中，我们鉴定出四个新的miRNA基因（MIR-107、MIR-130b、MIR-203a、MIR-1258），其在肿瘤组织中的甲基化率普遍较高（28%-52%），而在配对的组织学正常组织中为4%-7%，p<0.01。结果表明，MIR-130b、MIR-203a和MIR-1258基因的高甲基化与卵巢癌转移显著相关（p<0.05）。这些结果提示四种miRNA（miR-107、miR-130b、miR-203a和miR-1258）及其编码基因的高甲基化参与了卵巢癌的发病机制。