由于死亡率高,卵巢癌严重威胁着女性的健康。广泛的腹部转移和化疗耐药是卵巢癌死亡的主要原因。通过lncRNA测序,我们之前的研究鉴定了lncRNASLC25A21-AS1,它在化疗耐药的卵巢癌细胞中显著下调.在这项研究中,我们旨在评估SLC25A21-AS1在卵巢癌中的作用和机制。通过qRT-PCR和在线数据库GEPIA分析SLC25A21-AS1的表达。用CCK-8、transwell、和流式细胞术。通过RNA测序分析其具体机制,RNA结合蛋白免疫沉淀,救援实验,和生物信息学分析。SLC25A21-AS1在卵巢癌组织和细胞系中降低。SLC25A21-AS1的过表达增强了卵巢癌细胞对紫杉醇和顺铂的敏感性,抑制细胞增殖,入侵,和移民,而SLC25A21-AS1沉默表现出相反的效果。钾通道亚家族K成员4(KCNK4)在SLC25A21-AS1强制表达时显著上调。过表达KCNK4抑制细胞增殖,入侵,迁移能力,并增强卵巢癌细胞对紫杉醇和顺铂的敏感性。同时,KNCK4过表达挽救了SLC25A21-AS1沉默对细胞增殖的促进作用,入侵和迁移。此外,SLC25A21-AS1可与Zeste同源物2(EZH2)的转录因子增强子相互作用,而EZH2敲除增加了一些卵巢癌细胞系中KCNK4的表达。SLC25A21-AS1增强化疗敏感性,抑制增殖,迁移,和卵巢癌细胞的侵袭能力至少部分通过阻断EZH2介导的KCNK4沉默。
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.