CircCDKN2B-AS1 interacts with IMP3 to stabilize Hexokinase 2 mRNA and facilitate cervical squamous cellcarcinoma aerobic glycolysis progression

作者：Yanan Zhang, Lu Zhao, Shizhou Yang, Yixuan Cen, Tingjia Zhu, Lingfang Wang, Lili Xia, Yuwan Liu, Jian Zou, Junfen Xu, Yang Li, Xiaodong Cheng, Weiguo Lu, Xinyu Wang, Xing Xie · 发表于：Research Square · 年份：2020 · DOI：10.21203/rs.3.rs-49280/v2 · 被引用次数：3 · 研究领域：Circular RNAs in diseases、RNA modifications and cancer、Cancer-related molecular mechanisms research

Abstract Background: Circular RNAs (circRNAs) have been reported to play key roles in the development of various cancers. However, the biological functions and clinical significance of most circRNAs are still elusive. The purpose of this study was to explore the function and mechanism of a certain circRNA named circCDKN2B-AS1 in cervical cancer development and its potential value in the clinic. Methods: qRT-PCR was used to verify the expression level of circCDKN2B-AS1. CCK-8, Transwell, and flow cytometry (FCM) assays were performed to detect cellular proliferation, migration, and apoptosis, respectively. A Seahorse XFe96 Analyzer was used to measure glycolysis metabolism level. RNA pull-down, RNA immunoprecipitation (RIP), actinomycin-D addition assays and Western blotting were used to screen and elucidate the potential mechanisms involved. BALB/c nude mice and zebrafish embryos (AB, WT) were used as animal models to investigate tumorigenesis capability. 18 FDG-microPET/CT imaging and lactic acid (LA) and pyruvic acid (PA) content detection assays were used to detect the level of glucose metabolism in subcutaneous tumors from nude mice. Results: CircCDKN2B-AS1, a circular isoform of the long noncoding RNA (lncRNA) CDKN2B-AS1, was upregulated in cervical cancer and precancerous tissues. We found that circCDKN2B-AS1 associated with the IMP3 protein depending on a specific binding site and regulated the stability of Hexokinase 2 (HK2) mRNA, the rate-limiting enzyme of the aerob...