The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex

نویسندگان

چکیده

Abstract Background As a novel type of non-coding RNA, circular RNAs (circRNAs) play critical role in the initiation and development various diseases, including cancer. However, exact function circRNAs human cervical cancer remains largely unknown. Methods We identified circRNA signature upregulated between paired adjacent normal tissues. Using two different cohorts GEO database, total six were with fold change > 2, P < 0.05. Among these circRNAs, hsa_circ_0072088 (circZFR) was only exonic significantly overexpressed Functional experiments performed to investigate biological circZFR. Circ RNA pull-down, immunoprecipitation (circRIP) Co-immunoprecipitation (Co-IP) assays executed molecular mechanism underlying Results Functionally, circZFR knockdown represses proliferation, invasion, tumor growth. Furthermore, pull-down combined mass spectrometry unveil interactions Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, bound SSBP1, thereby promoting assembly CDK2/cyclin E1 complexes. The activation complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading cell cycle progression proliferation. Conclusion Our findings provide first evidence that is onco-circRNA might be potential biomarker therapeutic target for patients.

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ژورنال

عنوان ژورنال: Journal of Experimental & Clinical Cancer Research

سال: 2021

ISSN: ['1756-9966']

DOI: https://doi.org/10.1186/s13046-021-01849-2