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Ten Hypermethylated lncRNA Genes Are Specifically Involved in the Initiation, Progression, and Lymphatic and Peritoneal Metastasis of Epithelial Ovarian Cancerстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Braga Eleonora A., Burdennyy Alexey M., Uroshlev Leonid A., Zaichenko Danila M., Filippova Elena A., Lukina Svetlana S., Pronina Irina V., Astafeva Iana R., Fridman Marina V., Kazubskaya Tatiana P., Loginov Vitaly I., Dmitriev Alexey A., Moskovtsev Aleksey A., Kushlinskii Nikolay E.
- Журнал: International Journal of Molecular Sciences
- Том: 25
- Год издания: 2024
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Первая страница: 4
- Последняя страница: 32
- DOI: 10.3390/ijms252111843
- Аннотация: Abstract:OurworkaimedtoevaluateanddifferentiatetheroleoftenlncRNAgenes(GAS5,HAND2AS1,KCNK15-AS1,MAGI2-AS3,MEG3,SEMA3B-AS1,SNHG6,SSTR5-AS1,ZEB1-AS1,andZNF667-AS1) in the development and progression of epithelial ovarian cancer (EOC). Are presentative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation level so fall ten lncRNA genes in tumors compared to normal tissues (p < 0.001). Using RT-qPCR, we showed down regulation and an inverse relationship between methylation and expression levels for ten lncRNAs (rs <−0.5). We further identified lncRNA genes that were specifically hypermethylated in tumors from patients with metastasestolymphnodes(HAND2-AS1),peritoneum(KCNK15-AS1,MEG3,andSEMA3B-AS1),and greateromentum(MEG3,SEMA3B-AS1,andZNF667-AS1). The same four lncRNAgenesinvolvedin peritonealspreadwereassociatedwithclinicalstageandtumorextent(p<0.001). Interestingly, we found areversionfromincreasetodecreaseinthehypermethylationleveloffivemetastasis-relatedlncRNA genes (MEG3, SEMA3B-AS1, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in 59 peritoneal metastases. This reversion may be associated with partial epithelial–mesenchymal transition(EMT) in metastatic cells,asindicatedbyadecreaseintheleveloftheEMTmarker,CDH1mRNA(p<0.01). Furthermore, novel mRNA targets and regulated miRNAs were predicted for a number of the studied lncRNAsusing the NCBIGEO data sets and analyzed by RT-qPCR and transfection of SKOV3 and OVCAR3 cells. In addition, hypermethylation of SEMA3B-AS1,SSTR5-AS1,andZNF667-AS1geneswasproposedasa marker for overall survival in patients with EOC.
- Добавил в систему: Казубская Татьяна Павловна