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.
Electronic supplementary material
The online version of this article (10.1186/s12943-019-1037-8) contains supplementary material, which is available to authorized users.
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This paper considers the initial boundary value problem of solutions for a class of sixth order 1-D nonlinear wave equations. We discuss the probabilities of the existence and nonexistence of global solutions and give some sufficient conditions for the global and non-global existence of solutions at three different initial energy levels, i.e., sub-critical level, critical level and sup-critical level. 1. Introduction. In this paper, we consider the initial boundary value problem (IBVP) for the following 1-D nonlinear wave equation of sixth order u tt − au xx + u xxxx + u xxxxtt + f (u x) x = 0, (x, t) ∈ (0, 1) × (0, ∞), (1) u(x, 0) = u 0 (x), u t (x, 0) = u 1 (x), x ∈ [0, 1], (2)
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