Inhibition of ABI2 Ubiquitination-Dependent Degradation Suppresses Breast Cancer Cell Growth via Down-regulating PI3K/Akt Signaling Pathway [RNAseq-20240415]

TNBC is a type of cancer that lacks receptor expression and has complex molecular mechanisms. Recent evidence shows that the ubiquitin-protease system is closely related to TNBC. In this study, we obtain a key ubiquitination regulatory substrate-abi2 protein by bioinformatics methods, which is also closely related to the survival and prognosis of TNBC. Further, through a series of experiments, we demonstrated that ABI2 expressed at a low level in TNBC tumors, and it has the ability to control cell cycle and inhibit TNBC cell migration, invasion and proliferation. Molecular mechanism studies proved E3 ligase CBLC could increase the ubiquitination degradation of ABI2 protein. Meanwhile, RNA-seq and IP experiments indicated that ABI2 can significantly inhibit PI3K/Akt signaling pathway via the interaction with Rho GTPase RAC1. Finally, we also found that the antibiotic Colistimethate could inhibit the growth of TNBC cells by inhibiting CBLC-induced ABI2 ubiquitination and down-regulating PI3K/Akt signaling pathway. Overall design: To investigate the molecular mechanism of CS inhibiting the growth of TNBC cells, we performed RNA-seq analysis on MDA-MB-231 cells treated with Colistimethate at the dose of 20 µM. We performed gene expression profiling analysis using data obtained from RNA-seq of two different cells at three repeated experiments. Comparative gene expression profiling analysis of RNA-seq data for control MDA-MB-231 cells and Colistimethate treated MDA-MB-231 cells.