河北医学2025，Vol.31Issue(11)：1808-1815,8.DOI:10.3969/j.issn.1006-6233.2025.11.08
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
Study on the Mechanism of KCNK1 Activating PI3K/AKT Signaling Pathway to Promote the Metastatic Ability of Papillary Thyroid Carcinoma
摘要
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 param-eters 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 ex-periment.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 tran-scriptome sequencing technology,and conducting KEGG signaling pathway enrichment analysis.The modula-tory 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 pa-tients 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 ob-served 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 path-way 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.关键词
甲状腺乳头状癌/钾双孔域通道亚家族K成员1/转移/PI3K/AKT信号通路Key words
PTC/KCNK1/Transfer/PI3K/AKT signaling pathway引用本文复制引用
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):1808-1815,8.基金项目
广西自治区卫生健康委西医类自筹经费科研课题,(编号:Z-N20221875) （编号:Z-N20221875）
