Whole-Transcriptome Analysis of Docetaxel-Resistant LNCaP and C4-2B Prostate Cancer Cells Reveals Alternative Splicing and Non-Coding RNA Dimensions of Taxane Resistance

Docetaxel (DTX) is a first-line chemotherapy for metastatic castration-resistant prostate cancer, but acquired resistance is near-universal. We previously generated isogenic DTX-resistant LNCaP and C4-2B cell line derivatives and profiled them using Affymetrix Clariom D arrays, but our initial analysis was limited to gene-level differential expression highlighting ABCB1. Here, we re-analysed all twelve arrays (two lineages × parental/resistant × three passages) using a linear-model framework to exploit exon/junction-level and non-coding transcriptome data. We confirmed the core resistance signature (ABCB1, VTRNA1-1, TRAIL/TNFSF10) and identified a shared 587-gene resistance programme within which mitotic and microtubule-based-movement genes were coordinately down-regulated. Splice analysis revealed 315 high-confidence reciprocal exon-usage events (including NTNG1, CTNND1, MYO6, MAT2A). Biotype-resolved analysis identified 123 resistance-associated lncRNAs (including LINC00152/CYTOR), with co-regulated antisense/sense pairs (e.g., MME-AS1/MME, ATP1B3-AS1/ATP1B3) suggesting candidate local (sense–antisense) regulatory relationships. The proliferation programme aligned with growth kinetics, as cell-cycle/mitotic genes were down-regulated in slower-growing C4-2BR cells. By fully exploiting Clariom D, we extend the molecular portrait of DTX resistance beyond gene expression to coordinated alternative splicing and structured non-coding responses.