Abstract
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 (H2O2) 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.
Highlights
Colorectal cancer is the third most common type of cancer in the world[1,2]
Analysis of data extracted from the Oncomine database revealed a high correlation between Brother of Regulator of Imprinted Sites (BORIS) expression and colorectal cancer
To further verify the significance of BORIS in colorectal cancer, the expression and sub-cellular localization of BORIS were observed by immunohistochemistry (IHC) assay in 180 clinical colon samples, which included 100 cancer tissues and 80 adjacent normal tissues collected from 100 colon cancer patients (Table 1)
Summary
Colorectal cancer is the third most common type of cancer in the world[1,2]. Despite advances in colorectal cancer research and treatment, colorectal cancer remains incurable because of drug resistance[1,2,3]. In breast cancer, silencing of BORIS by short interfering RNA (siRNA) suppressed cancer cell viability and induced caspase 3/7 activity[15]. These findings suggest that aberrant expression of BORIS might suppress apoptosis in cancer cells. BORIS binds to RNA and associates with actively translating ribosomes[23] Both cytoplasm- and nucleus-localized BORIS are related to prostate cancer[24]. We identified the requirement of BORIS in colorectal cancer and provided direct evidence that zinc finger domains (ZF domains) deleted and cytoplasm-localized BORIS-ZFdel suppressed apoptosis. The cytoplasmic roles of BORIS in apoptotic inhibition highlights the potential clinical applications of BORIS for the treatment of colorectal cancer
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