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LncRNA SLC25A21-AS1 increases the chemosensitivity and inhibits the progression of ovarian cancer by upregulating the expression of KCNK4.
- Source :
-
Functional & integrative genomics [Funct Integr Genomics] 2023 Mar 30; Vol. 23 (2), pp. 110. Date of Electronic Publication: 2023 Mar 30. - Publication Year :
- 2023
-
Abstract
- Owing to high mortality rate, ovarian cancer seriously threatens women's health. Extensive abdominal metastasis and chemoresistance are the leading causes of ovarian cancer deaths. Through lncRNA sequencing, our previous study identified lncRNA SLC25A21-AS1, which was significantly downregulated in chemoresistant ovarian cancer cells. In this study, we aimed to evaluate the role and mechanism of SLC25A21-AS1 in ovarian cancer. The expression of SLC25A21-AS1 was analyzed by qRT-PCR and online database GEPIA. The biological functions of SLC25A21-AS1 and KCNK4 were analyzed by CCK-8, transwell, and flow cytometry. The specific mechanism was analyzed by RNA-sequencing, RNA binding protein immunoprecipitation, rescue experiments, and bioinformatic analysis. SLC25A21-AS1 was decreased in ovarian cancer tissues and cell lines. Overexpression of SLC25A21-AS1 enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin, and inhibited cell proliferation, invasion, and migration, while SLC25A21-AS1-silencing showed the opposite effect. Potassium channel subfamily K member 4 (KCNK4) was significantly up-regulated upon enforced expression of SLC25A21-AS1. Overexpression of KCNK4 inhibited cell proliferation, invasion, migration ability, and enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin. Meanwhile, KNCK4-overexpression rescued the promotive effect of SLC25A21-AS1-silencing on cell proliferation, invasion and migration. In addition, SLC25A21-AS1 could interact with the transcription factor Enhancer of Zeste Homolog 2 (EZH2), while EZH2 knockdown increased the expression of KCNK4 in some of the ovarian cancer cell lines. SLC25A21-AS1 enhanced the chemosensitivity and inhibited the proliferation, migration, and invasion ability of ovarian cancer cells at least partially by blocking EZH2-mediated silencing of KCNK4.<br /> (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Subjects :
- Humans
Female
Cell Line, Tumor
Cisplatin pharmacology
Cisplatin metabolism
Cell Proliferation genetics
Paclitaxel
Gene Expression Regulation, Neoplastic
Potassium Channels genetics
Potassium Channels metabolism
Ovarian Neoplasms drug therapy
Ovarian Neoplasms genetics
Ovarian Neoplasms metabolism
RNA, Long Noncoding genetics
RNA, Long Noncoding metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1438-7948
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Functional & integrative genomics
- Publication Type :
- Academic Journal
- Accession number :
- 36995496
- Full Text :
- https://doi.org/10.1007/s10142-023-01035-x