Exploring the Influence of Differentially Expressed Long Common Non-Coding RNAs on Palbociclib Resistance in Breast Cancer Cell Lines

Drug resistance is a common problem in both hormone receptor-positive and triple-negative breast cancers, posing significant challenges in effective treatment. Palbociclib, a CDK4/6 inhibitor, has emerged as a promising therapy for breast cancer by targeting cell cycle regulation, however, resistance to palbociclib frequently develops. This study investigates the role of long non-coding RNAs (IncRNAs) in palbociclib-resistant breast cancer, analyzing gene expression profiles from MDA-MB-231 (triple-negative) and MCF-7 (hormone receptor-positive) cell lines. Differential gene expression analysis, identified 152 IncRNAs that were common in both resistant cell lines. Genomic context and cis-regulatory elements associated with these IncRNAs were further examined, revealing 14 IncRNAs with specific genomic associations linked to chemotherapy resistance. Notably, MIR646HG is linked with both MCF-7 and MDA-MB-231 by influencing different Genomic contexts. Certain IncRNAs have been associated exclusively with either MCF-7 or MDA-MB-231 cell lines, while others are linked to both but show predominant expression in one of them. Our findings suggest that IncRNAs, through their interaction with key genomic contexts, may serve as potential therapeutic targets for overcoming palbociclib resistance in breast cancer subtypes.