Comparative RNA-seq analysis reveals potential mechanisms mediating the conversion to androgen independence in an LNCaP progression cell model

Abstract

The androgen-independent phenotype is an important symptom of refractory prostate cancer. However, the molecular mechanisms underlying this phenotypic conversion remain unclear. Using RNA-seq analysis of androgen-dependent prostate cancer cells (LNCaP) vs. androgen-independent cancer cells (LNCaP-AI-F), we identified 788 differentially expressed genes, 315 alternative splicing events, and eight novel LNCaP-AI-F-specific fusion genes. The fusion genes EIF2AK1-ATR and GLYR1-SLC9A8 were predicted to be damaging and oncogenic. We also observed dramatic changes in androgen receptor (AR)-mediated pathway molecules, including prostate-specific antigen (PSA, a major biomarker of prostate cancer) and AR variants, as well as neuroendocrine-like (NE-like) and tumor stem cell-like characteristics, during androgen-independent phenotype progression. Our findings provide new insights into the regulatory complexities of refractory prostate cancers.

Keywords: Alternative splicing; Androgen-independent; Fusion gene; Prostate cancer; RNA-seq; Tumor stem cell-like.