Center for Molecular Medicine, Zhejiang Academy of Medical Science, Hangzhou, Zhejiang Province, 310012, P.R. China.
Sci Rep. 2017 Jan 18;7:40786. doi: 10.1038/srep40786.
Identifying oncogenes that promote cancer cell proliferation or survival is critical for treatment of colorectal cancer. The Brother of Regulator of Imprinted Sites (BORIS) is frequently expressed in most types of cancer, but rarely in normal tissues. Aberrantly expressed BORIS relates to colorectal cancer, but its function in colorectal cancer cells remains unclear. In addition, previous studies indicated the significance of cytoplasm-localized BORIS in cancer cells. However, none of them investigated its function. Herein, we investigated the functions of BORIS in cancer cell proliferation and apoptosis and the role of cytoplasm-localized BORIS in colorectal cancer. BORIS expression correlated with colorectal cancer proliferation. BORIS overexpression promoted colorectal cancer cell growth, whereas BORIS knockdown suppressed cell proliferation. Sensitivity of colorectal cancer cells to 5-fluorouracil (5-FU) was inversely correlated with BORIS expression. These data suggest that BORIS functions as an oncogene in colorectal cancer. BORIS silencing induced reactive oxygen species (ROS) production and apoptosis, whereas BORIS supplementation inhibited apoptosis induced by BORIS short interfering RNA (siRNA), hydrogen peroxide (HO) or 5-FU. Introduction of BORIS-ZFdel showed that cytoplasmic localization of BORIS inhibited apoptosis but not ROS production. Our study highlights the anti-apoptotic function of BORIS in colorectal cancer.
鉴定促进癌细胞增殖或存活的致癌基因对于结直肠癌的治疗至关重要。印迹基因调控因子兄弟（BORIS）在大多数类型的癌症中频繁表达，但在正常组织中很少表达。异常表达的 BORIS 与结直肠癌有关，但它在结直肠癌细胞中的功能尚不清楚。此外，先前的研究表明细胞质定位的 BORIS 在癌细胞中的重要性。然而，它们都没有研究其功能。在此，我们研究了 BORIS 在癌细胞增殖和凋亡中的功能，以及细胞质定位的 BORIS 在结直肠癌中的作用。BORIS 的表达与结直肠癌的增殖相关。BORIS 的过表达促进结直肠癌细胞生长，而 BORIS 的敲低则抑制细胞增殖。结直肠癌细胞对 5-氟尿嘧啶（5-FU）的敏感性与 BORIS 的表达呈负相关。这些数据表明 BORIS 在结直肠癌中作为致癌基因发挥作用。BORIS 沉默诱导活性氧（ROS）的产生和凋亡，而 BORIS 补充则抑制 BORIS 小干扰 RNA（siRNA）、过氧化氢（HO）或 5-FU 诱导的凋亡。BORIS-ZFdel 的引入表明，BORIS 的细胞质定位抑制了凋亡而不抑制 ROS 的产生。我们的研究强调了 BORIS 在结直肠癌中的抗凋亡功能。
