AUTHOR=Chen Quanfang , Pan Qingyun , Gao Han , Wang Yingju , Zhong Xiaoning 

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

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.878947

DOI=10.3389/fneur.2022.878947

ISSN=1664-2295

ABSTRACT=<sec><title>Objectives</title><p>Present 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.</p></sec><sec><title>Methods</title><p>Transcriptome 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 <italic>HCP5</italic> /hsa-miR-17-5p/<italic>HOXA7</italic> axis for analysis. Further, a clinical cohort was employed to validate the regulatory roles of molecules involved in the ceRNA regulatory axis.</p></sec><sec><title>Results</title><p>Here 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 (<italic>HOXA7, TBX5</italic>, and <italic>TCF21</italic>), and five lncRNAs (<italic>HCP5, LINC00460, TP53TG1</italic>). Using gene set enrichment analysis (GSEA) and survival analysis, the potential axis of <italic>HCP5</italic> /hsa-miR-17-5p/<italic>HOXA7</italic> was further investigated. It is found that <italic>HOXA7</italic> and ferroptosis index are positively correlated while inhibiting tumor brain metastasis. It may be that <italic>HCP5</italic> binds competitively with miR-17-5p and upregulates <italic>HOXA7</italic> to increase iron death limiting brain cancer metastases</p></sec><sec><title>Conclusions</title><p>The expression of both <italic>HOXA7</italic> and <italic>HCP5</italic> is positively correlated with FPI, indicating a possible link between ferroptosis and BNM. According to the results of our study, the ferroptosis-related ceRNA <italic>HCP5</italic> /hsa-miR-17-5p/<italic>HOXA7</italic> axis may contribute to the development of BNM in LUAD patients.</p></sec>