Hypermethylation of Genes in New Long Noncoding RNA in Ovarian Tumors and Metastases: A Dual Effect

被引:9
作者
Burdennyy, A. M. [1 ]
Filippova, E. A. [1 ]
Ivanova, N. A. [1 ]
Lukina, S. S. [1 ]
Pronina, I. V. [1 ]
Loginov, V. I. [1 ]
Fridman, M. V. [2 ]
Kazubskaya, T. P. [3 ]
Utkin, D. O. [3 ]
Braga, E. A. [1 ]
Kushlinskii, N. E. [3 ]
机构
[1] Res Inst Gen Pathol & Pathophysiol, Moscow, Russia
[2] Russian Acad Sci, NI Vavilov Inst Gen Genet, Moscow, Russia
[3] NN Blokhin Natl Med Res Ctr Oncol, Minist Hlth Russian Federat, Moscow, Russia
关键词
long non-coding RNA; methylation; ovarian cancer; metastases; genes SEMA3B-AS1; TINCR; and ZNF667-AS1; INVASION; CANCER;
D O I
10.1007/s10517-021-05230-3
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:370 / 374
页数:5
相关论文
共 14 条
[1]  
[Anonymous], 2014, CLASSIFICATION TUMOU
[2]   LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms [J].
Braga, Eleonora A. ;
Fridman, Marina, V ;
Moscovtsev, Alexey A. ;
Filippova, Elena A. ;
Dmitriev, Alexey A. ;
Kushlinskii, Nikolay E. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (22) :1-44
[3]   lncRNA mortal obligate RNA transcript was downregulated in ovarian carcinoma and inhibits cancer cell proliferation by downregulating miRNA-21 [J].
Chen, Xiao ;
Wu, Wanyin ;
Cao, Xiaolong ;
Zhao, Xiaoshan ;
Li, Weizhan ;
Deng, Caijiu ;
Huang, Zhen .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2019, 120 (07) :11949-11954
[4]   Epithelial mesenchymal transition in ovarian carcinoma [J].
Davidson, Ben ;
Trope, Claes G. ;
Reich, Reuven .
FRONTIERS IN ONCOLOGY, 2012, 2
[5]   MiR-6872 host gene SEMA3B and its antisense lncRNA SEMA3B-AS1 function synergistically to suppress gastric cardia adenocarcinoma progression [J].
Guo, Wei ;
Liang, Xiaoliang ;
Liu, Lei ;
Guo, Yanli ;
Shen, Supeng ;
Liang, Jia ;
Dong, Zhiming .
GASTRIC CANCER, 2019, 22 (04) :705-722
[6]   A methylation-specific and SYBR-green-based quantitative polymerase chain reaction technique for O6-methylguanine DNA methyltransferase promoter methylation analysis [J].
Hattermann, Kirsten ;
Mehdorn, H. Maximilian ;
Mentlein, Rolf ;
Schultka, Susann ;
Held-Feindt, Janka .
ANALYTICAL BIOCHEMISTRY, 2008, 377 (01) :62-71
[7]   RETRACTED: Silencing the long noncoding RNA, TINCR, a molecular sponge of miR-335, inhibits the malignant phenotype of epithelial ovarian cancer via FGF2 suppression (Retracted article. See vol. 61, pg. 121, 2022) [J].
Li, Rui ;
Wang, Yue ;
Xu, Yuexun ;
He, Xiaoli ;
Li, Yali .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2019, 55 (05) :1110-1124
[8]   TINCR suppresses proliferation and invasion through regulating miR-544a/FBXW7 axis in lung cancer [J].
Liu, Xiaochun ;
Ma, Jing ;
Xu, Feng ;
Li, Li .
BIOMEDICINE & PHARMACOTHERAPY, 2018, 99 :9-17
[9]   Novel miRNA genes deregulated by aberrant methylation in ovarian carcinoma are involved in metastasis [J].
Loginov, Vitaly I. ;
Pronina, Irina V. ;
Burdennyy, Alexey M. ;
Filippova, Elena A. ;
Kazubskaya, Tatiana P. ;
Kushlinsky, Dmitry N. ;
Utkin, Dmitry O. ;
Khodyrev, Dmitry S. ;
Kushlinskii, Nikolay E. ;
Dmitriev, Alexey A. ;
Braga, Eleonora A. .
GENE, 2018, 662 :28-36
[10]   Long non-coding RNA GAS5 inhibits ovarian cancer cell proliferation via the control of microRNA-21 and SPRY2 expression [J].
Ma, Nana ;
Li, Shaoru ;
Zhang, Quanhua ;
Wang, Hongmei ;
Qin, Haixia ;
Wang, Shijin .
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2018, 16 (01) :73-82