Tian Kui, Tao Zhenggui, Chen Yu, Du Jinghu, Chen Manyu, Wang Donghua, Li Zijia
Department of Colorectal Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Art and Science, Xiangyang, Hubei, China.
Department of Colorectal Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Art and Science, Xiangyang, Hubei, China.
Pathol Res Pract. 2023 Jan;241:154234. doi: 10.1016/j.prp.2022.154234. Epub 2022 Nov 19.
Colorectal cancer (CRC) is a common malignancy, and radioresistance limits the effectiveness of radiotherapy for rectal cancer. This study is performed to investigate the role and regulatory mechanism of Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 4 (KCNE4) in the radioresistance of CRC cells.
Immunohistochemical staining results of KCNE4 in normal tissues and CRC tissues were obtained from the Human Protein Atlas (HPA) database. The UALCAN database was used for analyzing KCNE4 mRNA expression in normal tissue samples and CRC tissue samples and its relationship with tumor stage. The relationship of KCNE4 expression with prognosis was analyzed utilizing the data of GEPIA database. LinkedOmics database was searched to analyze the co-expressed gene sets of KCNE4 in CRC, and to analyze the signaling pathways related with KCNE4 in CRC. GO and KEGG enrichment analyses were carried out on the co-expressed genes of KCNE4 with DAVID database. Ionizing radiation (IR)-resistant cell lines (HCT116/IR and HT29/IR) were established; cell viability was assessed via cell counting kit-8 (CCK-8) and EdU assays, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was performed for detecting cell apoptosis. Western blotting was carried out to detect the expressions of p-p85 and p-AKT.
KCNE4 was highly expressed in CRC tissues and linked to advanced tumor stage, lymph node metastasis and poor prognosis of CRC patients. KCNE4 overexpression promoted HCT116/IR cell proliferation and inhibited the apoptosis, while KCNE4 knockdown suppressed HT29/IR cell proliferation and facilitated the apoptosis. Furthermore, high KCNE4 expression was associated with the activation of the PI3K/AKT signal pathway.
KCNE4 is associated with the clinicopathological characteristics of CRC patients, and its high expression level contributes to the radioresistance of cancer cells via activating the PI3K/AKT signal pathway.
结直肠癌（CRC）是一种常见的恶性肿瘤，放射抗性限制了直肠癌放射治疗的效果。本研究旨在探讨钾离子电压门控通道亚家族E调节亚基4（KCNE4）在CRC细胞放射抗性中的作用及调控机制。
从人类蛋白质图谱（HPA）数据库获取正常组织和CRC组织中KCNE4的免疫组化染色结果。使用UALCAN数据库分析正常组织样本和CRC组织样本中KCNE4 mRNA表达及其与肿瘤分期的关系。利用GEPIA数据库的数据分析KCNE4表达与预后的关系。搜索LinkedOmics数据库以分析CRC中KCNE4的共表达基因集，并分析CRC中与KCNE4相关的信号通路。使用DAVID数据库对KCNE4的共表达基因进行GO和KEGG富集分析。建立电离辐射（IR）抗性细胞系（HCT116/IR和HT29/IR）；通过细胞计数试剂盒-8（CCK-8）和EdU试验评估细胞活力，并进行末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）试验检测细胞凋亡。进行蛋白质免疫印迹法检测p-p85和p-AKT的表达。
KCNE4在CRC组织中高表达，与CRC患者的肿瘤晚期、淋巴结转移和预后不良相关。KCNE4过表达促进HCT116/IR细胞增殖并抑制凋亡，而KCNE4敲低抑制HT29/IR细胞增殖并促进凋亡。此外，KCNE4高表达与PI3K/AKT信号通路的激活相关。
KCNE4与CRC患者的临床病理特征相关，其高表达水平通过激活PI3K/AKT信号通路促进癌细胞的放射抗性。
