Journal Article

A novel AR translational regulator lncRNA LBCS inhibits castration resistance of prostate cancer

Huang, Jian, Lin, Tianxin, Liu, Xiaodong, Huang, Li, Dong, Wen, Xie, Ruihui, Xie, Weibin, Gu, Peng, Han, Jinli, Chen, Xu, Shen, Jihong

2019

Overview

Background Progression to a castration resistance state is the main cause of deaths in prostate cancer (PCa) patients. Androgen Receptor (AR) signaling plays the central role in progression of Castration Resistant Prostate Cancer (CRPC), therefore understanding the mechanisms of AR activation in the milieu of low androgen is critical to discover novel approach to treat CRPC. Methods Firstly, we explore the CRPC associated lncRNAs by transcriptome microarray. The expression and clinical features of lnc-LBCS are analyzed in three independent large-scale cohorts. The functional role and mechanism of lnc-LBCS are further investigated by gain and loss of function assays in vitro. Results The expression of Lnc-LBCS was lower in CRPC cells lines and tissues. LBCS downregulation was correlated with higher Gleason Score, T stage and poor prognosis of PCa patients. LBCS overexpression decreases, whereas LBCS knockdown increases, the traits of castration resistance in prostate cancer cells under androgen ablated or AR blocked condition. Moreover, knockdown of LBCS was sufficient to activate AR signaling in the absence of androgen by elevating the translation of AR protein. Mechanistically, LBCS interacted directly with hnRNPK to suppress AR translation efficiency by forming complex with hnRNPK and AR mRNA. Conclusions Lnc-LBCS functions as a novel AR translational regulator that suppresses castration resistance of prostate cancer by interacting with hnRNPK. This sheds a new insight into the regulation of CRPC by lncRNA mediated AR activation and LBCS-hnRNPK-AR axis provides a promising approach to the treatment of CRPC.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 5' Untranslated Regions / Androgen receptor (AR) / Androgen receptors / Androgen suppression therapy / Androgens / Biomedical and Life Sciences / Biomedicine / Bladder cancer / Cancer cells / Cancer patients / Cancer Research / Care and treatment / Castration / Castration resistance / Castration resistance prostate Cancer (CRPC) / Cell cycle / Cell Line, Tumor / Development and progression / DNA microarrays / Gene expression / Gene Expression Profiling - methods / Gene Expression Regulation, Neoplastic / Genetic aspects / Heterogeneous-Nuclear Ribonucleoprotein K - genetics / hnRNPK / Humans / lncRNA LBCS / Male / Medical prognosis / Messenger RNA / Metastasis / MicroRNAs - genetics / Neoplasm Staging / Oligonucleotide Array Sequence Analysis / Oncology / Patient outcomes / Patients / Phenols / Prognosis / Prostate cancer / Prostatic Neoplasms, Castration-Resistant - genetics / Prostatic Neoplasms, Castration-Resistant - pathology / Proteins / Receptors, Androgen - genetics / RNA / Survival Analysis / Translation / Translation (Genetics)