Chen Fang, Yin Yinghao, Yan Zhifeng, Cao Ke, Zhong Kuangbiao
Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
Oncol Lett. 2018 Mar;15(3):2921-2928. doi: 10.3892/ol.2017.7670. Epub 2017 Dec 20.
Nucleus accumbens-associated protein 1 (NAC1), a transcriptional co-regulator, is overexpressed in advanced prostate cancer. However, the NAC1-regulated transcriptome has not been completely explored. In the present study, the functional silencing of NAC1 blocked the migration of prostate cancer cells and suppress osteoclastogenesis. The present study also determined that NAC1 was overexpressed in the highly aggressive prostate cancer cell lines PC-3, DU-145 and LNCaP. NAC1 small interfering RNA treatment of DU-145 cells decreased cell migration, but interestingly had no significant effects on cell proliferation. Furthermore, microarray analysis showed that a group of genes may be associated with the development of prostate cancer after NAC1 knockdown, including interferon-β (IFNβ), which is reported to be involved in osteoclastogenesis, an important factor affecting bone metastasis. The mechanisms of NAC1 function were further explored by co-culture studies using PC-3 and RAW264.7 osteoclast precursor cells, which demonstrated that silencing NAC1 downregulated the genes associated with the activation of osteoclasts. Furthermore, it was revealed that NAC1 had the ability to affect the release of IFNβ into the extracellular environment. Together, these findings indicated that NAC1 promoted cell migration, and that NAC1 may have a key role in osteoclastogenesis.
伏隔核相关蛋白1（NAC1）是一种转录共调节因子，在晚期前列腺癌中过表达。然而，NAC1调节的转录组尚未得到充分研究。在本研究中，NAC1的功能沉默阻断了前列腺癌细胞的迁移并抑制破骨细胞生成。本研究还确定NAC1在高侵袭性前列腺癌细胞系PC-3、DU-145和LNCaP中过表达。用NAC1小干扰RNA处理DU-145细胞可降低细胞迁移，但有趣的是对细胞增殖没有显著影响。此外，微阵列分析表明，一组基因可能与NAC1敲低后前列腺癌的发展有关，包括干扰素-β（IFNβ），据报道它参与破骨细胞生成，是影响骨转移的一个重要因素。通过使用PC-3和RAW264.7破骨细胞前体细胞的共培养研究进一步探索了NAC1的功能机制，结果表明沉默NAC1可下调与破骨细胞激活相关的基因。此外，研究发现NAC1能够影响IFNβ释放到细胞外环境中。总之，这些发现表明NAC1促进细胞迁移，并且NAC1可能在破骨细胞生成中起关键作用。
