title: 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.
authors.affiliation: Behavioral Genetics Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China; Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Fengbiao
authors.initials: F
authors.lastname: Mao
authors.forename: Tingting
authors.initials: T
authors.lastname: Qin
authors.forename: Huajing
authors.initials: H
authors.lastname: Teng
authors.forename: Wanshi
authors.initials: W
authors.lastname: Cai
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.forename: Zhong Sheng
authors.initials: ZS
authors.lastname: Sun
authors.forename: Congying
authors.initials: C
authors.lastname: Xie
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D010641:Phenotype; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger
keywords: Alternative splicing; Androgen-independent; Fusion gene; Prostate cancer; RNA-seq; Tumor stem cell-like