Functional And Mechanism Of Micropeptide CIP2A-BP Encoded By LncRNA LINC00665 In TNBC

Background:Triple negative breast cancer(TNBC)is a recurrent and more aggressive subtype of breast cancer.Currently,there is still no effective targeted therapy for triple negative breast cancer.Long non-coding RNA(lncRNA)usually regulates the physiological and pathological processes of the body at the transcriptional and translation level in the form of RNA.However,little is known about the role of bioactive micropeptides encoded by IncRNA in a variety of cellular activities.In triple negative breast cancer,the mechanism of micropeptides produced by IncRNA coding needs to be further explored.Methods:Bioinformatics analysis,Polysome profiling experiment and real-time PCR(qPCR)were used to screen the target IncRNA.The endogenous expression,regulatory mechanism and functional mechanism of CIP2A-BP were studied by Western blot,immunofluorescence,ChIP,luciferase report experiment,immunoprecipitation(co-IP)and mass spectrometry(MS)analysis.Cell and animal experiments were used to verify the effect of target lncRNA coding product on triple negative breast cancer cells.Survival analysis was carried out by Kaplan-Meier method.Results:Transforming growth factor β(TGF-β)activated Smad signaling pathway,promoted the expression of translation inhibitory protein 4E-BP1 and decreased the micropeptide CIP2A-BP encoded by LINC00665.In cell and animal experiments,it was found that micropeptide CIP2A-BP inhibited the invasion and metastasis of triple negative breast cancer cells.Immunoprecipitation.mass spectrometry and subsequent Western blot experiments showed that CIP2A-BP directly binds to CIP2A,replaces the B56 y subunit of PP2A,releases PP2A activity and suppresses PI3K/Akt/NFκB pathway.The down-regulation of CIP2A-BP expression in TNBC patients was significantly correlated with tumor metastasis and overall survival rate.Conclusion:Micropeptide CIP2A-BP is not only a prognostic marker but also a new potential therapeutic target for triple negative breast cancer.