Department of Colorectal Surgery, Zhengzhou Central Hospital Affiliated To Zhengzhou University, 16 Tongbai North Road, Zhengzhou, Henan, China.
BMC Med Genomics. 2022 Sep 13;15(1):194. doi: 10.1186/s12920-022-01351-4.
This study attempted to verify the potential of KCNJ14 as a biomarker in colorectal cancer (CRC).
Data on transcriptomics and DNA methylation and the clinical information of CRC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Biological information analysis methods were conducted to determine the role of KCNJ14 in the prognosis, diagnosis, immune cell infiltration, and regulation mechanism of CRC patients. The effect of KCNJ14 on the proliferation and migration of HCT116 and SW480 CRC cell lines was verified by in vitro experiments (MTT, colony-forming, wound healing, and transwell assays). Western blotting was performed to detect the effect of KCNJ14 on the levels of mTOR signalling pathway-related proteins.
KCNJ14 expression was remarkably increased in CRC tissues and cell lines, which reduced the overall survival time of patients. KCNJ14 mRNA was negatively regulated by its methylation site cg17660703, which can also endanger the prognosis of patients with CRC. Functional enrichment analysis suggested that KCNJ14 is involved in the mTOR, NOD-like receptor, and VEGF signalling pathways. KCNJ14 expression was positively correlated with the number of CD4 + T cells and negatively correlated with that of CD8 + T cells in the immune microenvironment. KCNJ14 knockdown significantly reduced not only the proliferation and migration of CRC cell lines but also the levels of mTOR signalling pathway-related proteins.
This study not only increases the molecular understanding of KCNJ14 but also provides a potentially valuable biological target for the treatment of colorectal cancer.
本研究旨在验证 KCNJ14 作为结直肠癌（CRC）生物标志物的潜力。
从癌症基因组图谱和基因表达综合数据库中下载了转录组学和 DNA 甲基化数据以及 CRC 患者的临床信息。采用生物信息学分析方法确定 KCNJ14 在 CRC 患者的预后、诊断、免疫细胞浸润和调控机制中的作用。通过体外实验（MTT、集落形成、划痕愈合和 Transwell 检测）验证 KCNJ14 对 HCT116 和 SW480 CRC 细胞系增殖和迁移的影响。采用 Western blot 检测 KCNJ14 对 mTOR 信号通路相关蛋白水平的影响。
KCNJ14 在 CRC 组织和细胞系中表达显著增加，降低了患者的总生存时间。KCNJ14 的 mRNA 受其甲基化位点 cg17660703 的负调控，也会危及 CRC 患者的预后。功能富集分析表明，KCNJ14 参与 mTOR、NOD 样受体和 VEGF 信号通路。KCNJ14 表达与免疫微环境中 CD4 + T 细胞的数量呈正相关，与 CD8 + T 细胞的数量呈负相关。KCNJ14 敲低不仅显著降低了 CRC 细胞系的增殖和迁移能力，而且降低了 mTOR 信号通路相关蛋白的水平。
本研究不仅增加了对 KCNJ14 的分子认识，而且为结直肠癌的治疗提供了一个有潜在价值的生物学靶点。
