The Second Department of Gynecology, Cangzhou Central Hospital, 16 Xinhua West Road, Cangzhou, 061000, China.
The Second Department of Gynecology, Cangzhou Central Hospital, 16 Xinhua West Road, Cangzhou, 061000, China.
Biomed Pharmacother. 2020 Jun;126:110085. doi: 10.1016/j.biopha.2020.110085. Epub 2020 Mar 18.
The promoting effects of transcriptional factor Yin Yang 1 (YY1) have been confirmed in various tumors, however, its roles in ovarian cancer (OC) progression are still unclear. Here, Kaplan-Meier Plotter analysis was used to determine the correlation between YY1 expression and the survival of OC patients. It was found that YY1 expression was negatively correlated with the overall survival, progression-free survival and post-progression survival of OC patients. Functional experiments indicated that overexpression of YY1 facilitated the stemness of OC cells, while YY1 knockdown reduced it. MiRNAs-based RNA-sequencing analysis showed that miR-99a was the mostly upregulated miRNA in RNA extracted from OC cells with YY1 knockdown. Mechanistic studies revealed that YY1 recruited (Histone deacetylase) HDAC5 to the promoter of miR-99a, and subsequently enhanced miR-99a deacetylation level and decreased miR-99a level. Additionally, overexpression of miR-99a or knockdown of HDAC5 attenuated the promoting effects of YY1 on the stemness of OC cells. This work firstly indicated a novel YY1/miR-99a axis, which promotes the stemness of OC cells.
转录因子 Yin Yang 1 (YY1) 的促进作用已在各种肿瘤中得到证实,然而,其在卵巢癌 (OC) 进展中的作用尚不清楚。在这里,Kaplan-Meier Plotter 分析用于确定 YY1 表达与 OC 患者生存之间的相关性。结果发现,YY1 表达与 OC 患者的总生存期、无进展生存期和进展后生存期呈负相关。功能实验表明,YY1 的过表达促进了 OC 细胞的干性,而 YY1 的敲低则降低了其干性。基于 miRNA 的 RNA-seq 分析显示,在 YY1 敲低的 OC 细胞中提取的 RNA 中,miR-99a 是上调最多的 miRNA。机制研究表明,YY1 将 (Histone deacetylase) HDAC5 募集到 miR-99a 的启动子上,随后增强了 miR-99a 的去乙酰化水平并降低了 miR-99a 的水平。此外,miR-99a 的过表达或 HDAC5 的敲低减弱了 YY1 对 OC 细胞干性的促进作用。这项工作首次表明了一个新的 YY1/miR-99a 轴,它促进了 OC 细胞的干性。