KLF5 facilitates lung adenocarcinoma metastasis via regulating the epithelial-mesenchymal transition pathway through RHPN2

Background Distant metastasis is the primary reason shortening the survival time for patients with advanced lung adenocarcinoma. Transcription factor Kruppel-like factor 5 (KLF5) has been confirmed to facilitate the progression of lung adenocarcinoma. However, the certain mechanism by which KLF5 involves in the tumor metastasis of lung adenocarcinoma remains largely unclear. Methods Gpt-ho-binding Protein 2 (RHPN2) was screened as the potential downstream target gene for KLF5 via bioinformatics analysis, which closely participates in regulation of the epithelial mesenchymal transformation (EMT) pathway in lung adenocarcinoma. Western blot and immunohistochemistry assays 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 cell growth and metastasis of lung adenocarcinoma. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to analyze the direct binding activity between the KLF5 and RHPN2 promoter regions. The luciferase activity assay was carried out to verify the transcriptional activation effect of KLF5 to RHPH2. Results RHPN2 was found to be highly expressed in lung adenocarcinoma and patients with highly RHPN2 expression showed a poor prognosis in lung adenocarcinoma. In vivo and in vitro, experiments identified that RHPN2 promoted the cell growth and metastasis, and activated the EMT pathway in lung adenocarcinoma. Machanismly, KLF5 could directly bind to the promoter regions of RHPN2 and up-regulate the expression of the latter in lung adenocarcinoma through translational activation. In addition, the rescue experiments confirmed that RHPN2 facilitated the progression of lung adenocarcinoma at least in a KLF5-dependent form. Conclusion Our study offers insights into the potential mechanisms of metastasis in lung adenocarcinoma and suggests RHPN2 as a potential therapeutic target.