MiR-17-5p/HOXA7 Is a Potential Driver for Brain Metastasis of Lung Adenocarcinoma Related to Ferroptosis Revealed by Bioinformatic Analysis.

Abstract

ObjectivesPresent study aims to identify the essential mRNAs responsible for the development of brain neurovascular-related metastases (BNM) among lung adenocarcinoma (LUAD) patients. Further, we attempted to predict brain metastases more accurately and prevent their development in LUAD patients.MethodsTranscriptome data analysis was used to identify differentially expressed mRNAs (DEMs) associated with brain metastasis, and thereby the ferroptosis index (FPI) is calculated using a computational model. Meanwhile, the DEmRNAs linked with FPI, and brain metastasis were derived by the intersection of these two groups of DEMs. We also constructed a ceRNA network containing these DEmRNAs, identifying the HCP5 /hsa-miR-17-5p/HOXA7 axis for analysis. Further, a clinical cohort was employed to validate the regulatory roles of molecules involved in the ceRNA regulatory axis.ResultsHere we report the development of a ceRNA network based on BNM-associated DEMs and FPI-associated DEmRNAs which includes three core miRNAs (hsa-miR-338-3p, hsa-miR-429, and hsa-miR-17-5p), three mRNAs (HOXA7, TBX5, and TCF21), and five lncRNAs (HCP5, LINC00460, TP53TG1). Using gene set enrichment analysis (GSEA) and survival analysis, the potential axis of HCP5 /hsa-miR-17-5p/HOXA7 was further investigated. It is found that HOXA7 and ferroptosis index are positively correlated while inhibiting tumor brain metastasis. It may be that HCP5 binds competitively with miR-17-5p and upregulates HOXA7 to increase iron death limiting brain cancer metastasesConclusionsThe expression of both HOXA7 and HCP5 is positively correlated with FPI, indicating a possible link between ferroptosis and BNM. According to the results of our study, the ferroptosis-related ceRNA HCP5 /hsa-miR-17-5p/HOXA7 axis may contribute to the development of BNM in LUAD patients.