Journal Article

lncRNA HOXD-AS1 Regulates Proliferation and Chemo-Resistance of Castration-Resistant Prostate Cancer via Recruiting WDR5

Huang, Jian, Chen, Changhao, Han, Jinli, Chen, Xu, Lin, Tianxin, Wang, Bo, Dong, Wen, Jiang, Junyi, Xie, Ruihui, Xie, Weibin, Gu, Peng, Yang, Meihua, Chen, Ziyue

2017

Overview

Castration-resistant prostate cancer (CRPC) that occurs after the failure of androgen deprivation therapy is the leading cause of deaths in prostate cancer patients. Thus, there is an obvious and urgent need to fully understand the mechanism of CRPC and discover novel therapeutic targets. Long noncoding RNAs (lncRNAs) are crucial regulators in many human cancers, yet their potential roles and molecular mechanisms in CRPC are poorly understood. In this study, we discovered that an lncRNA HOXD-AS1 is highly expressed in CRPC cells and correlated closely with Gleason score, T stage, lymph nodes metastasis, and progression-free survival. Knockdown of HOXD-AS1 inhibited the proliferation and chemo-resistance of CRPC cells in vitro and in vivo. Furthermore, we identified several cell cycle, chemo-resistance, and castration-resistance-related genes, including PLK1, AURKA, CDC25C, FOXM1, and UBE2C, that were activated transcriptionally by HOXD-AS1. Further investigation revealed that HOXD-AS1 recruited WDR5 to directly regulate the expression of target genes by mediating histone H3 lysine 4 tri-methylation (H3K4me3). In conclusion, our findings indicate that HOXD-AS1 promotes proliferation, castration resistance, and chemo-resistance in prostate cancer by recruiting WDR5. This sheds a new insight into the regulation of CRPC by lncRNA and provides a potential approach for the treatment of CRPC. [Display omitted] Huang, Lin, and colleagues show that long noncoding RNA HOXD-AS1 is upregulated in castration-resistant prostate cancer (CRPC) and correlated with disease progression. HOXD-AS1 promotes proliferation, castration resistance, and chemo-resistance of prostate cancer cells via interacting with WDR5, which in turn activates the transcription of downstream genes.

• Publisher: Elsevier Inc,Elsevier Limited,American Society of Gene & Cell Therapy
• Subject: Adult / Aged / Androgens / Antineoplastic Agents - pharmacology / AURKA / Biomarkers, Tumor / Bladder cancer / Cancer therapies / Castration / castration-resistant prostate cancer / Cell cycle / Cell Cycle - genetics / Cell Line, Tumor / Cell Movement - genetics / Cell proliferation / Cell Proliferation - genetics / Cell Transformation, Neoplastic - genetics / chemo-resistance / CRPC / DNA Methylation / Drug Resistance, Neoplasm - genetics / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Gene Knockdown Techniques / Grants / Higher education / Histone H3 / Histone-Lysine N-Methyltransferase - genetics / Humans / Kinases / Laboratories / long noncoding RNA HOXD-AS1 / Lymph nodes / Lysine / Male / Medical prognosis / Metastases / Metastasis / Middle Aged / Molecular modelling / Neoplasm Grading / Neoplasm Metastasis / Neoplasm Staging / Original / PLK1 / Polo-like kinase 1 / Promoter Regions, Genetic / Prostate cancer / Prostatic Neoplasms, Castration-Resistant - genetics / Prostatic Neoplasms, Castration-Resistant - mortality / Prostatic Neoplasms, Castration-Resistant - pathology / Prostatic Neoplasms, Castration-Resistant - therapy / Proteins / RNA Interference / RNA, Long Noncoding - genetics / Therapeutic applications / Transcription / Tumors / WDR5