Oncogenic Role of BOLL in Colorectal Cancer.

Boule-like RNA-binding protein (BOLL protein) is the progenitor of the Deleted in Azoospermia (DAZ) gene family. To date, previous studies have focused on the reproductive function of BOLL. While we were identifying new DNA methylation biomarkers for colorectal cancer (CRC), we found that BOLL protein was overexpressed in CRC. The aim of this study was to determine the role of BOLL in CRC by epigenetic and functional studies in vivo and in vitro. BOLL promoter methylation and expression were determined by MethyLight, RT-PCR, Western blot, and immunohistochemistry. The functional role of BOLL in CRC was evaluated by cell proliferation, colony formation, migration and invasion, cell cycle status, and tumor growth in a xenograft model. BOLL promoter methylation was enhanced in CRC tissues compared with normal colorectal tissues [97/124 (78 %) vs. 2/124 (2 %)]. However, the mean immunoreactivity score of CRC tissues and paired adjacent normal tissues was 8.15 ± 0.18 (SD) and 3.35 ± 0.19 (SD), respectively (p < 0.01). No significant association was observed between immunoreactivity score and clinicopathological parameters, including age, gender, tumor size, tumor differentiation, and tumor node metastasis stage. Expression of BOLL in CRC cell lines significantly enhanced cell proliferation (p < 0.01), colony formation (p < 0.01), and migration (p < 0.01). In BOLL-expressing cells, the percentage of cells in S-phase of the cell cycle was significantly increased. Tumor volume in BOLL xenografted mice was significantly enhanced after subcutaneous implantation (p < 0.01). Our study demonstrated an oncogenic role of BOLL in CRC despite tumor-specific promoter hypermethylation.