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Hypermethylation of Genes in New Long Noncoding RNA in Ovarian Tumors and Metastases: A Dual Effect
Bulletin of Experimental Biology and Medicine ( IF 0.9 ) Pub Date : 2021-07-22 , DOI: 10.1007/s10517-021-05230-3
A M Burdennyy 1 , E A Filippova 1 , N A Ivanova 1 , S S Lukina 1 , I V Pronina 1 , V I Loginov 1 , M V Fridman 2 , T P Kazubskaya 3 , D O Utkin 3 , E A Braga 1 , N E Kushlinskii 3
Affiliation  

The role of methylation in the regulation of genes of long noncoding RNA (lncRNA) is still poorly understood. We revealed new hypermethylated lncRNA genes in ovarian tumors and their effect on metastasis of ovarian cancer. A multiple and significant (p<0.001) increase in methylation of a group of lncRNA genes (MEG3, SEMA3B-AS1, ZNF667-AS1, and TINCR) was shown by quantitative methylation-specific PCR using the non-parametric Mann—Whitney test. Moreover, methylation of SEMA3B-AS1, ZNF667-AS1, and TINCR genes in ovarian cancer tumors was detected for the first time. Comparative analysis of 19 samples of peritoneal metastases and paired primary tumors showed a significant decrease in the methylation level of the same 4 genes: MEG3 (p=0.004), SEMA3B-AS1 (p=0.002), TINCR (p=0.002), and ZNF667-AS1 (p<0.001). Reduced methylation of suppressor lncRNA genes in peritoneal metastases is probably associated with the involvement of these lncRNA in the regulation of plastic reversion of the epithelial-mesenchymal transition to the mesenchymal-epithelial transition. Thus, the effect of lncRNA and their methylation on the development of tumors and metastases of ovarian cancer was demonstrated, which is important for understanding of the pathogenesis and mechanisms of metastasis of ovarian cancer. New properties of lncRNA can find application in the development of new approaches in the therapy of ovarian cancer.



中文翻译:

卵巢肿瘤和转移瘤中新长链非编码 RNA 基因的高甲基化:双重效应

甲基化在调控长链非编码 RNA (lncRNA) 基因中的作用仍然知之甚少。我们揭示了卵巢肿瘤中新的高甲基化 lncRNA 基因及其对卵巢癌转移的影响。使用非参数 Mann-Whitney 检验的定量甲基化特异性 PCR 显示了一组 lncRNA 基因(MEG3SEMA3B - AS1ZNF667 - AS1TINCR)甲基化的多重显着 ( p <0.001) 增加。此外,SEMA3B-AS1ZNF667 - AS1TINCR 的甲基化首次检测到卵巢癌肿瘤中的基因。对 19 个腹膜转移灶和成对原发肿瘤样本的比较分析显示,相同 4 个基因的甲基化水平显着降低:MEG3 ( p =0.004)、SEMA3B-AS1 ( p =0.002)、TINCR ( p =0.002) 和ZNF667-AS1 ( p<0.001)。腹膜转移瘤中抑制性 lncRNA 基因甲基化减少可能与这些 lncRNA 参与调节上皮-间质转化为间充质-上皮转化的可塑性逆转有关。从而证实了lncRNA及其甲基化对卵巢癌肿瘤发展和转移的影响,这对于了解卵巢癌的发病机制和转移机制具有重要意义。lncRNA的新特性可用于开发治疗卵巢癌的新方法。

更新日期:2021-07-22
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