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KLF5 facilitates lung adenocarcinoma metastasis by regulating the epithelial-mesenchymal transition pathway through RHPN2  ( SCI-EXPANDED收录)  

文献类型:期刊文献

英文题名:KLF5 facilitates lung adenocarcinoma metastasis by regulating the epithelial-mesenchymal transition pathway through RHPN2

作者:Zhang, Tao[1,2];Wang, Ruo-qi[3];Yang, Yu-bin[3];Zhao, Wen-jun[2];Zhang, Qi-dong[2];Ma, Xu-li[2];Guo, Juan-juan[3];Su, Qian[2];Shen, Xiao-yun[3];Lu, Yong-bin[4];Su, Fei[1,2];Hou, Xiao-ming[1,2,3]

第一作者:Zhang, Tao

通信作者:Su, F[1];Hou, XM[1];Su, F[2];Hou, XM[2];Hou, XM[3];Lu, YB[4]

机构:[1]Lanzhou Univ, Hosp 1, Dept Oncol, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[4]Lanzhou Univ, Evidence Based Med Ctr, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China

第一机构:Lanzhou Univ, Hosp 1, Dept Oncol, Lanzhou 730000, Gansu, Peoples R China

通信机构:[1]corresponding author), Lanzhou Univ, Hosp 1, Dept Oncol, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Gansu, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[4]corresponding author), Lanzhou Univ, Evidence Based Med Ctr, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份:2025

卷号:23

期号:1

外文期刊名:JOURNAL OF TRANSLATIONAL MEDICINE

收录:;Scopus(收录号:2-s2.0-105018397753);WOS:【SCI-EXPANDED(收录号:WOS:001591874300005)】;

基金:We thank Professor Ran-ran sun for his guidance and assistance in animal experiments. ChIP-qPCR service was provided by Shanghai Cutseq Biomedical Technology Co., Ltd. We also acknowledge TCGA, GEO and JASPAR database for providing their platforms and contributors for uploading their meaningful datasets.

语种:英文

外文关键词:Lung adenocarcinoma; RHPN2; KLF5; EMT; Metastasis; Transcription

摘要:BackgroundDistant metastasis is a primary factor contributing to the significantly shorter survival time of patients with advanced lung adenocarcinoma. The transcription factor Kruppel-like factor 5 (KLF5) facilitates the progression of lung adenocarcinoma. However, the specific mechanism by which KLF5 is involved in the tumor metastasis of lung adenocarcinoma metastasis remains largely unclear.MethodsUsing bioinformatic analysis, Rhophilin Rho GTPase Binding Protein 2 (RHPN2) was identified as a potential downstream target gene for KLF5; it plays a crucial role in the regulation of the epithelial-mesenchymal transformation pathway in lung adenocarcinoma. Western blotting and immunohistochemistry were performed to examine RHPN2 expression in lung adenocarcinoma. In vivo and in vitro experiments were conducted to explore the regulatory role of RHPN2 on the cell growth and metastasis of lung adenocarcinoma. Chromatin immunoprecipitation sequencing was used to analyze the direct binding activity between KLF5 and RHPN2 promoter regions. Luciferase activity assay was performed to verify the transcriptional activation effect of KLF5 on RHPH2.ResultsRHPN2 was highly expressed in lung adenocarcinoma; patients with lung adenocarcinoma who showed high RHPN2 expression had a poor prognosis. In vivo and in vitro experiments showed that RHPN2 promoted cell growth and metastasis and activated the epithelial-mesenchymal transformation pathway in lung adenocarcinoma. KLF5 directly bound to the promoter region of RHPN2 and upregulated its expression in lung adenocarcinoma through transcriptional activation. In addition, rescue experiments confirmed that KLF5 facilitated the progression of lung adenocarcinoma in an RHPN2-dependent manner.ConclusionOur study offers insights into the potential mechanisms of metastasis in lung adenocarcinoma and highlights RHPN2 as a potential therapeutic target.

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