Mingyi Zhou1, Zhuo Yang1, Danbo Wang2, Peng Chen1, Yong Zhang3. 1. Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, Liaoning Province, People's Republic of China. 2. Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, Liaoning Province, People's Republic of China. wangdanbo@cancerhosp-ln-cmu.com. 3. Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, China.
Abstract
BACKGROUND: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. METHODS: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR. RESULTS: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. CONCLUSION: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.
BACKGROUND: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in humancervical cancer remains largely unknown. METHODS: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR. RESULTS: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. CONCLUSION: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancerpatients.
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