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http://purl.uniprot.org/citations/37705041http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37705041http://www.w3.org/2000/01/rdf-schema#comment"

Background

Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with a poor prognosis. The underlying functions and mechanisms of circular RNA and SUMOylation in the development of ICC remain poorly understood.

Methods

Circular RNA hsa_circ_0001681 (termed Circ-RAPGEF5 hereafter) was identified by circular RNA sequencing from 19 pairs of ICC and adjacent tissue samples. The biological function of Circ-RAPGEF5 in tumor proliferation and metastasis was examined by a series of in vitro assays. A preclinical model was used to validate the therapeutic effect of targeting Circ-RAPGEF5. RNA pull-down and dual-luciferase reporter assays were used to access the RNA interactions. Western blot and Co-IP assays were used to detect SUMOylation levels.

Results

Circ-RAPGEF5, which is generated from exons 2 to 6 of the host gene RAPGEF5, was upregulated in ICC. In vitro and in vivo assays showed that Circ-RAPGEF5 promoted ICC tumor proliferation and metastasis, and inhibited apoptosis. Additionally, high Circ-RAPGEF5 expression was significantly correlated with a poor prognosis. Further investigation showed that SAE1, a potential target of Circ-RAPGEF5, was also associated with poor oncological outcomes. RNA pull-down and dual-luciferase reporter assays showed an interaction of miR-3185 with Circ-RAPGEF5 and SAE1. Co-IP and western blot assays showed that Circ-RAPGEF5 is capable of regulating SUMOylation.

Conclusion

Circ-RAPGEF5 promotes ICC tumor progression and SUMOylation by acting as a sponge for miR-3185 to stabilize SAE1. Targeting Circ-RAPGEF5 or SAE1 might be a novel diagnostic and therapeutic strategy in ICC."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.org/dc/terms/identifier"doi:10.1186/s13046-023-02813-y"xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Chen T."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Li S."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Liang X."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Pan H."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Sun Y."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Tao L."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Wang Y."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Ruan Y."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Xu J."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Zheng J."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Ye Z."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Shen Z."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Cai J."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/author"Lin K."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/name"J Exp Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/pages"239"xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/title"Circ-RAPGEF5 promotes intrahepatic cholangiocarcinoma progression by stabilizing SAE1 to facilitate SUMOylation."xsd:string
http://purl.uniprot.org/citations/37705041http://purl.uniprot.org/core/volume"42"xsd:string
http://purl.uniprot.org/citations/37705041http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/37705041
http://purl.uniprot.org/citations/37705041http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/37705041
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