ABSTRACT

Emerging reports have indicated that long non-coding RNAs (lncRNAs) play pivotal roles in multiple cancers, containing cervical cancer. LncRNA ARAP1 antisense RNA 1 (ARAP1-AS1) was previously identified as a tumor-promoter in bladder cancer. However, the expression profile and possible modulation mechanism of ARAP1-AS1 in cervical cancer need to be further studied. In the current research, ARAP1-AS1 was discovered to exhibit a high level in cervical cancer cells. Besides, the knockdown of ARAP1-AS1 repressed cell proliferative and migratory capacities in cervical cancer, as detected by loss-of-function assays including CCK-8, EdU, colony formation, and transwell assays. Additionally, dual-specificity phosphatase 5 (DUSP5), lowly expressed in cervical cancer cells, was found to be negatively modulated by ARAP1-AS1. In subsequence, mechanism experiments proved that ARAP1-AS1 recruited enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) to regulate DUSP5 expression. Finally, rescue assays certified the oncogenic function of ARAP1-AS1/EZH2/DUSP5 axis in cervical cancer. This research probed the expression level and regulatory mechanism of ARAP1-AS1 underlying cervical cancer, which might shed novel lights into the exploration on cervical cancer treatment.

摘要

新出现的报告表明，长链非编码 RNA (lncRNAs) 在包括宫颈癌在内的多种癌症中发挥着关键作用。LncRNA ARAP1 反义 RNA 1 (ARAP1-AS1) 先前被鉴定为膀胱癌的肿瘤启动子。然而，ARAP1-AS1在宫颈癌中的表达谱和可能的调控机制有待进一步研究。在目前的研究中，发现 ARAP1-AS1 在宫颈癌细胞中表现出高水平。此外，ARAP1-AS1 的敲低抑制了宫颈癌中的细胞增殖和迁移能力，如通过功能丧失检测（包括 CCK-8、EdU、集落形成和 transwell 检测）检测到的。此外，发现在宫颈癌细胞中低表达的双特异性磷酸酶 5 (DUSP5) 受到 ARAP1-AS1 的负调节。随后，机制实验证明ARAP1-AS1募集zeste 2多梳抑制复合物2亚基（EZH2）的增强子来调节DUSP5的表达。最后，救援分析证实了 ARAP1-AS1/EZH2/DUSP5 轴在宫颈癌中的致癌功能。本研究探讨了宫颈癌相关ARAP1-AS1的表达水平及调控机制，为探索宫颈癌治疗提供了新的思路。