Qian Yu, Xia Suhua, Feng Zhenyu
Translational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
Biochem Biophys Res Commun. 2017 Jan 29;483(1):475-481. doi: 10.1016/j.bbrc.2016.12.119. Epub 2016 Dec 19.
FOXK2, which belongs to the fork head DNA binding protein family, has been shown to play a critical role in tumorigenesis. Here, we detected FOXK2 expression and its clinical significance in colorectal cancer, which has not been fully investigated before. Results from public database and our cohort indicated that FOXK2 was transcriptionally activated in colorectal cancer tissues compared to non-cancer tissues. High expression of FOXK2 was significantly correlated with poor survival. In vitro cell experiments suggested that FOXK2 promoted cell proliferation. Furthermore, we found that oncogene SOX9 was responsible for the up-regulation of FOXK2 by directly binding on its promoter. Depletion of FOXK2 attenuated SOX9 induced cell growth. In addition, we observed that the expression of FOXK2 was significantly associated with the expression of SOX9 both in the public database and our colorectal cancer tissues. The patients with SOX9FOXK2 had a poor overall survival (p = 0.0084). In conclusion, our data suggested that SOX9 transcriptionally activated FOXK2 was involved in the pathogenesis of colorectal cancer and might be a novel target for colorectal cancer therapy.
FOXK2属于叉头DNA结合蛋白家族，已被证明在肿瘤发生中起关键作用。在此，我们检测了FOXK2在结直肠癌中的表达及其临床意义，此前尚未对此进行充分研究。公共数据库和我们队列的结果表明，与非癌组织相比，FOXK2在结直肠癌组织中被转录激活。FOXK2的高表达与较差的生存率显著相关。体外细胞实验表明，FOXK2促进细胞增殖。此外，我们发现癌基因SOX9通过直接结合其启动子导致FOXK2上调。敲低FOXK2可减弱SOX9诱导的细胞生长。此外，我们观察到在公共数据库和我们的结直肠癌组织中，FOXK2的表达均与SOX9的表达显著相关。SOX9和FOXK2均高表达的患者总生存率较差（p = 0.0084）。总之，我们的数据表明，SOX9转录激活的FOXK2参与了结直肠癌的发病机制，可能是结直肠癌治疗的新靶点。
