Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave., 510515, Guangzhou, Guangdong Province, China.
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave., 510515, Guangzhou, Guangdong Province, China.
Cell Death Dis. 2019 Nov 13;10(11):863. doi: 10.1038/s41419-019-2046-7.
Aberrant gene expression plays critical roles in the development of colorectal cancer (CRC). Here we show that POTEE, which was identified as a member E of POTE ankyrin domain family, was significantly upregulated in colorectal tumors and predicted poor overall survival of CRC patients. In CRC cells, POTEE could act as an oncogene and could promote cell growth, cell-cycle progression, inhibit apoptosis, and elevates xenograft tumor growth. Mechanically, we used microarray analysis and identified a POTEE/SPHK1/p65 signaling axis, which affected the biological functions of CRC cells. Further evaluation showed that overexpression of POTEE could increase the protein expression of SPHK1, followed by promoting the phosphorylation and activation of p65 protein. Altogether, our findings suggested a POTEE/SPHK1/p65 signaling axis could promote colorectal tumorigenesis and POTEE might potentially serve as a novel biomarker for the diagnosis and an intervention of colorectal cancer.
异常基因表达在结直肠癌（CRC）的发生发展中起着关键作用。在这里，我们发现 POTEE 作为 POTE 锚蛋白结构域家族的 E 成员，在结直肠肿瘤中显著上调，并预测 CRC 患者的总生存率较差。在 CRC 细胞中，POTEE 可以作为癌基因，促进细胞生长、细胞周期进程、抑制细胞凋亡，并提高异种移植肿瘤的生长。在机制上，我们利用微阵列分析鉴定了一个 POTEE/SPHK1/p65 信号轴，该信号轴影响 CRC 细胞的生物学功能。进一步的评估表明，POTEE 的过表达可以增加 SPHK1 的蛋白表达，进而促进 p65 蛋白的磷酸化和激活。总的来说，我们的研究结果表明，POTEE/SPHK1/p65 信号轴可以促进结直肠肿瘤的发生，POTEE 可能作为结直肠癌诊断和干预的新的生物标志物。
