IncRNA HOXD-AS1 Regulates Proliferation and Chemo-Resistance of Castration-Resistant Prostate Cancer via Recruiting WDR5
IncRNA HOXD-AS1 Regulates Proliferation and Chemo-Resistance of Castration-Resistant Prostate Cancer via Recruiting WDR5
复制标题
IncRNA HOXD-AS1 通过招募 WDR5 调节去势抵抗性前列腺癌的增殖和化疗耐药性
DOI：
10.1016/j.ymthe.2017.04.016
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发表时间：
2017-08-02
影响因子：
12.4
通讯作者：
Lin, Tianxin
中科院分区：
文献类型：
--
作者：
Gu, Peng;Chen, Xu;Lin, Tianxin
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 IncRNA 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 invitro and in vivo. Furthermore, we identified several cell cycle, chemo-resistance, and castration-resistance related genes, including PLK1, AURKA, CDC25C, FOXM1, and VBE2C, 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 IncRNA and provides a potential approach for the treatment of CRPC.
