Circ-RAPGEF5 promotes intrahepatic cholangiocarcinoma progression by stabilizing SAE1 to facilitate SUMOylation

Circ-RAPGEF5 promotes intrahepatic cholangiocarcinoma progression by stabilizing SAE1 to facilitate SUMOylation

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Abstract 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 30hh bikini 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 ucsb gaucho blue 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.