摘要目的: 研究钾双孔域通道亚家族K成员1(potassium two pore domain channel subfamily K member 1,KCNK1)在甲状腺乳头状癌 ( papillary thyroid cancer,PTC)中的表达、与患者临床病理参数的关系及促进PTC细胞转移能力的作用机制。方法: 收集我院2019年1月至2020年12月从PTC患者切除的癌组织及癌旁组织85例。采用免疫组织化学(IHC)检测PTC癌和癌旁组织中KCNK1的表达,并分析其表达水平与患者临床病理参数及预后的关系。Western-blot检测KCNK1在PTC各细胞系(KTC-1,IHH-4,TPC-1)中的表达,选择KCNK1高表达的PTC细胞系TPC-1分为shNC组、shKCNK1-1组和shKCNK1-2组,Western-blot检测各组细胞中KCNK1的表达;Transwell实验和划痕实验检测各组细胞转移能力;Western-blot检测各组细胞中E-cadherin和N-cadherin蛋白表达;shNC组和shKCNK1-1组差异表达基因采用全转录组测序技术分析,并进行KEGG信号通路富集;Western-blot和功能实验检测KCNK1对PI3K/AKT信号通路的调控作用。结果: 与癌旁组织相比,PTC组织中KCNK1阳性率增加(50.59% VS 21.18%;χ2=15.98,P=0.000),KCNK1阳性率在淋巴结转移、癌浸润周围组织和TNM分期晚期的PTC患者中表达增加(P<0.05),KCNK1阳性表达的PTC患者预后较差(复发转移率34.88% VS 14.29%;χ2=4.842,P=0.028)。与人正常的甲状腺滤泡上皮细胞系Nthyori3-1相比,KCNK1在PTC细胞系中表达增加,在TPC-1细胞中的表达最高(P<0.05)。TPC-1细胞转染KCNK1敲减慢病毒,与shNC组相比,shKCNK1-1组和shKCNK1-2组细胞中KCNK1蛋白表达降低(P<0.05),shKCNK1-1组和shKCNK1-2组细胞转移能力降低(P<0.05),KEGG信号通路富集分析显示shNC组和shKCNK1-1组差异表达基因富集在PI3K/AKT信号通路,与shNC组相比,shKCNK1-1组细胞中pPI3K,pAKT蛋白表达降低(P<0.05)。AKT激动剂SC79激活shKCNK1-1组细胞PI3K/AKT信号通路活性,可以减弱敲减KCNK1对PTC细胞转移能力的抑制作用(P<0.05)。结论: KCNK1在PTC中表达增加,与临床病理参数及不良预后相关,敲减KCNK1抑制PI3K/AKT信号通路抑制PTC细胞转移能力。
Abstract：Objective: To investigate the expression of potassium two pore domain channel subfamily K member 1 (KCNK1) in papillary thyroid cancer (PTC), and its relationship with clinical pathological parameters of patients, and its mechanism of promoting PTC cell metastasis. Methods: Totally 85 cases of cancer tissue and adjacent tissue removed from PTC patients in our hospital from January 2019 to December 2020 were collected. The expression of KCNK1 in PTC and adjacent tissues was detected by immunohistochemistry (IHC), to analyse the relationship between KCNK1 expression and patients’ clinical pathological parameters, prognosis. Western blot was used to detect the expression of KCNK1 in various PTC cell lines(KTC-1, IHH-4, TPC-1). PTC cell lines TPC-1 with high expression of KCNK1 were selected and divided into shNC group, shKCNK1-1 group, and shKCNK1-2 group. KCNK1 expression in each group of cells was detected by western blot. The cell metastasis ability of each group was detected by transwell experiment and scratch experiment. E-cadherin and N-cadherin protein expression in each group of cells was detected by western blot. Differentially expressed genes between the shNC group and shKCNK1-1 group were analyzed by whole transcriptome sequencing technology, and conducting KEGG signaling pathway enrichment analysis. The modulatory role of KCNK1 in regulating the PI3K/AKT signaling pathway was detected by western blot and functional experiments. Results: Compared with adjacent cancer tissues, the positivity rate of KCNK1 increased in PTC tissues (50.59% VS 21.18%;χ2=15.98,P=0.000). The positivity rate of KCNK1 increased in PTC patients with lymph node metastasis, cancer infiltration surrounding tissues, and advanced TNM staging (P<0.05). PTC patients with KCNK1 positive expression had a poorer prognosis (recurrence and metastasis rate 34.88% VS 14.29%;χ2=4.842,P=0.028). Compared with the normal human thyroid follicular epithelial cell line Nthyori3-1, KCNK1 expression was higher in PTC cell lines, and the highest expression was observed in TPC-1 cells (P<0.05). TPC-1 cells transfected with KCNK1 knockdown virus showed a decrease in KCNK1 expression in shKCNK1-1 and shKCNK1-2 cells compared to the shNC group (P<0.05), as well as a decrease in cell metastasis ability (P<0.05). The differentially expressed genes between the shNC group and the shKCNK1-1 group were concentrated within the PI3K/AKT signaling pathway revealed by the KEGG signaling pathway enrichment analysis. The expression of pPI3K and pAKT proteins was reduced in shKCNK1-1 cells compared to the shNC group (P<0.05). AKT agonist SC79 activates the PI3K/AKT signaling pathway activity in shKCNK1-1 group cells, which can weaken the inhibitory effect of knocking down KCNK1 on the metastatic ability of PTC cells. Conclusion: KCNK1 expression increases in PTC and is associated with clinical pathological parameters and poor prognosis. Knocking down KCNK1 inhibits the PI3K/AKT signaling pathway and suppresses the metastatic ability of PTC cells.
黄廪春, 王建华, 李毅清, 杨立健, 劳景茂. KCNK1激活PI3K/AKT信号通路促进甲状腺乳头状癌转移能力的作用机制研究[J]. 河北医学, 2025, 31(11): 1808-1814.
HUANG Linchun, WANG Jianhua, LI Yiqing, et al. Study on the Mechanism of KCNK1 Activating PI3K/AKT Signaling Pathway to Promote the Metastatic Ability of Papillary Thyroid Carcinoma. HeBei Med, 2025, 31(11): 1808-1814.
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2025, Vol. 31 
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