Unlocking the aggressive potential of ZNF217 Exon-4 Skipping isoform in breast cancer and its contribution to bone metastasis

Breast cancer remains a major health concern worldwide, with bone metastases presenting a significant threat to patient outcomes. Generation of aberrant splicing variants with oncogenic potential are involved in the development and progression of tumors. this study identifies ZNF217-ΔE4 as a new oncogenic splice variant in breast cancer mediating cell aggressiveness and bone marrow homing, as well as a new indicator of the development of bone metastases. ZNF217-ΔE4 thus represents a novel candidate therapeutic target and a new valuable biomarker in the management of breast cancers, particularly in patients with a higher risk of developing bone metastases To investigate the role of ZNF217 variant splicing as (ZNF217-deltaE4 variant), HEK293 cells line have been transfected ina stable manner with vector containing 1) WT ZNF217 gene (called WT group) 2) Vector alone (called CMV group) 3) DeltaE4 ZNF217 variant (called DE group) 4) G1013 ZNF217 variant (called GLY group) Transcriptomic analysis by RNA seq has been realised on 12 samples (3 replicats for each group) (WT1, WT2, WT3); (CMV1,CMV2, CMV3); (DE1, DE2, DE3); (GLY1, GLY2, GLY3) RNAseq has been performed using DNBseq-G400 from MGI. Libraires have been constructed using the MGIEasy RNA Directional Library Prep Set (MGI). Single read of 100 bases has been realised. Diffrential expression between groups have been realised using Partek Software with CPM normalisation and DEseq pipeline. Functional analysis was performed with Panther software.