Colorectal cancer (CRC) is commonly associated with aberrant transcription regulation, but characteristics of the dysregulated transcription factors in CRC pathogenesis remain to be elucidated. In the present study, core-binding factor β (CBFβ) is found to be significantly upregulated in human CRC tissues and correlates with poor survival rate of CRC patients. Mechanistically, CBFβ is found to promote CRC cell proliferation, migration, invasion, and inhibit cell apoptosis in a RUNX2-dependent way. Transcriptome studies reveal that CBFβ and RUNX2 form a transcriptional complex that activates gene expression of OPN, FAM129A, and UPP1. Furthermore, CBFβ significantly promotes CRC tumor growth and live metastasis in a mouse xenograft model and a mouse liver metastasis model. In addition, tumor-suppressive miR-143/145 are found to inhibit CBFβ expression by specifically targeting its 3′-UTR region. Consistently, an inverse correlation between miR-143/miR-145 and CBFβ expression levels is present in CRC patients. Taken together, this study uncovers a novel regulatory role of CBFβ-RUNX2 complex in the transcriptional activation of OPN, FAM129A, and UPP1 during CRC development, and may provide important insights into CRC pathogenesis.

结直肠癌 (CRC) 通常与异常的转录调节有关，但 CRC 发病机制中失调的转录因子的特征仍有待阐明。在本研究中，发现核心结合因子 β (CBFβ) 在人类 CRC 组织中显着上调，并且与 CRC 患者的低存活率相关。从机制上讲，发现 CBFβ 以 RUNX2 依赖性方式促进 CRC 细胞增殖、迁移、侵袭和抑制细胞凋亡。转录组研究表明，CBFβ 和 RUNX2 形成转录复合物，可激活 OPN、FAM129A 和 UPP1 的基因表达。此外，CBFβ 在小鼠异种移植模型和小鼠肝转移模型中显着促进 CRC 肿瘤生长和活转移。此外，肿瘤抑制性 miR-143/145 被发现通过特异性靶向其 3'-UTR 区域来抑制 CBFβ 表达。一致地，CRC 患者中存在 miR-143/miR-145 和 CBFβ 表达水平之间的负相关。综上所述，本研究揭示了 CBFβ-RUNX2 复合物在 CRC 发展过程中 OPN、FAM129A 和 UPP1 转录激活中的新调节作用，并可能为 CRC 发病机制提供重要见解。