Transcriptional Profiling of CENPA-Depleted Prostate Cancer Cell Lines. Transcriptional Profiling of CENPA-Depleted Prostate Cancer Cell Lines

Overexpression of centromeric proteins has been identified in a number of human malignancies, though their functional and mechanistic contributions to disease progression have not been characterized. CENPA, the centromeric histone H3 variant, is the epigenetic mark that determines centromere identity. Here, we demonstrate that CENPA is highly overexpressed in prostate cancer in both tissue and cell lines, and the level of CENPA expression correlates with the stage of disease. Gain-of- and loss-of-function experimentation confirms that CENPA promotes prostate cancer cell line growth. Integrated sequencing studies further reveal a previously unidentified function of CENPA as a transcriptional regulator that modulates expression of critical proliferation, cell-cycle, and centromere/kinetochore genes. Our findings, therefore, suggest a previously undescribed biological function for CENPA, a protein normally thought to be solely and importantly involved in centromere identity. Overall design: Examination of transcriptional profile of prostate cancer cells under CENPA-depleted condtions

多种人类恶性肿瘤中均已检测到着丝粒蛋白（centromeric proteins）的过表达现象，但此类蛋白在疾病进展中的功能与机制贡献尚未得到阐明。CENPA，即着丝粒组蛋白H3变体（centromeric histone H3 variant），是决定着丝粒身份的表观遗传标记。本研究证实，CENPA在前列腺癌组织与细胞系中均呈高过表达状态，且其表达水平与疾病分期呈显著相关。功能获得（gain-of-function）与功能缺失（loss-of-function）实验证实，CENPA可促进前列腺癌细胞系的增殖。整合测序分析进一步揭示了CENPA此前未被发现的新功能：作为转录调控因子，其可调控关键增殖、细胞周期及着丝粒/动粒（centromere/kinetochore）相关基因的表达。因此，本研究结果揭示了CENPA此前未被报道的生物学功能——此前学界普遍认为CENPA仅且主要参与着丝粒身份的维持。实验设计：分析CENPA敲低（CENPA-depleted）条件下前列腺癌细胞的转录组谱。