Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments

BackgroundFerroptosis-related genes have been reported to play important roles in many diseases, but their molecular mechanisms in osteoporosis have not been elucidated.MethodsBased on two independent GEO datasets (GSE35956 and GSE35958), and GSE35959 as the validation dataset, we comprehensively el...

Full description

Saved in:
Bibliographic Details
Main Authors: Sihui Chen, Yi Jiang, Guoqin Xie, Peng Wu, Jinyu Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2024.1522809/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846091446374891520
author Sihui Chen
Sihui Chen
Yi Jiang
Yi Jiang
Guoqin Xie
Guoqin Xie
Peng Wu
Peng Wu
Jinyu Zhu
Jinyu Zhu
author_facet Sihui Chen
Sihui Chen
Yi Jiang
Yi Jiang
Guoqin Xie
Guoqin Xie
Peng Wu
Peng Wu
Jinyu Zhu
Jinyu Zhu
author_sort Sihui Chen
collection DOAJ
description BackgroundFerroptosis-related genes have been reported to play important roles in many diseases, but their molecular mechanisms in osteoporosis have not been elucidated.MethodsBased on two independent GEO datasets (GSE35956 and GSE35958), and GSE35959 as the validation dataset, we comprehensively elucidated the pathological mechanism of ferroptosis-related genes in osteoporosis by GO analyses, KEGG analyses and a PPI network. Then, We used Western Blot (WB) and Quantitative real-time polymerase chain reaction (qPCR) to verify the expression level of KMT2D, a ferroptosis-related hub gene, in clinical samples. Subsequently, we predicted the upstream miRNA of KMT2D gene and analyzed the mechanism of KMT2D in osteoporosis, the potential prognostic value and its immune invasion of KMT2D in pan-cancer.ResultsThis study identified KMT2D and MYCN, TP63, RELA, SOX2, and CDKN1A as key ferroptosis-related genes in osteoporotic cell aging. The independent dataset validated that the expression level of KMT2D was significantly upregulated in osteoporosis samples. The experimental verification results of qPCR and WB indicate that KMT2D is highly expressed in patients with osteoporosis. Further analysis revealed that the hsa-miR-204-5p-KMT2D axis may play an important role in the aging of osteoporotic cells. The analysis of KMT2D reveals that KMT2D may mainly play a role in the aging of osteoporotic cells through epigenetics and the value in pan-cancer.ConclusionThe study provides a theoretical basis for the treatment of osteoporosis.
format Article
id doaj-art-86666a37e3d54e7d89047ad3cf5bc458
institution Kabale University
issn 1664-8021
language English
publishDate 2025-01-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Genetics
spelling doaj-art-86666a37e3d54e7d89047ad3cf5bc4582025-01-10T06:10:30ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011510.3389/fgene.2024.15228091522809Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experimentsSihui Chen0Sihui Chen1Yi Jiang2Yi Jiang3Guoqin Xie4Guoqin Xie5Peng Wu6Peng Wu7Jinyu Zhu8Jinyu Zhu9Department of Orthopedics, First Hospital of Jiaxing, Jiaxing, ChinaCollege of Medicine, Jiaxing University, Jiaxing, ChinaDepartment of Orthopedics, First Hospital of Jiaxing, Jiaxing, ChinaCollege of Medicine, Jiaxing University, Jiaxing, ChinaDepartment of Orthopedics, First Hospital of Jiaxing, Jiaxing, ChinaCollege of Medicine, Jiaxing University, Jiaxing, ChinaDepartment of Orthopedics, First Hospital of Jiaxing, Jiaxing, ChinaCollege of Medicine, Jiaxing University, Jiaxing, ChinaDepartment of Orthopedics, First Hospital of Jiaxing, Jiaxing, ChinaCollege of Medicine, Jiaxing University, Jiaxing, ChinaBackgroundFerroptosis-related genes have been reported to play important roles in many diseases, but their molecular mechanisms in osteoporosis have not been elucidated.MethodsBased on two independent GEO datasets (GSE35956 and GSE35958), and GSE35959 as the validation dataset, we comprehensively elucidated the pathological mechanism of ferroptosis-related genes in osteoporosis by GO analyses, KEGG analyses and a PPI network. Then, We used Western Blot (WB) and Quantitative real-time polymerase chain reaction (qPCR) to verify the expression level of KMT2D, a ferroptosis-related hub gene, in clinical samples. Subsequently, we predicted the upstream miRNA of KMT2D gene and analyzed the mechanism of KMT2D in osteoporosis, the potential prognostic value and its immune invasion of KMT2D in pan-cancer.ResultsThis study identified KMT2D and MYCN, TP63, RELA, SOX2, and CDKN1A as key ferroptosis-related genes in osteoporotic cell aging. The independent dataset validated that the expression level of KMT2D was significantly upregulated in osteoporosis samples. The experimental verification results of qPCR and WB indicate that KMT2D is highly expressed in patients with osteoporosis. Further analysis revealed that the hsa-miR-204-5p-KMT2D axis may play an important role in the aging of osteoporotic cells. The analysis of KMT2D reveals that KMT2D may mainly play a role in the aging of osteoporotic cells through epigenetics and the value in pan-cancer.ConclusionThe study provides a theoretical basis for the treatment of osteoporosis.https://www.frontiersin.org/articles/10.3389/fgene.2024.1522809/fullKMT2DosteoporosisferroptosisagingBMSCs
spellingShingle Sihui Chen
Sihui Chen
Yi Jiang
Yi Jiang
Guoqin Xie
Guoqin Xie
Peng Wu
Peng Wu
Jinyu Zhu
Jinyu Zhu
Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments
Frontiers in Genetics
KMT2D
osteoporosis
ferroptosis
aging
BMSCs
title Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments
title_full Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments
title_fullStr Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments
title_full_unstemmed Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments
title_short Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments
title_sort comprehensive analysis of ferroptosis related genes reveals potential therapeutic targets in osteoporosis patients a computational analysis and in vitro experiments
topic KMT2D
osteoporosis
ferroptosis
aging
BMSCs
url https://www.frontiersin.org/articles/10.3389/fgene.2024.1522809/full
work_keys_str_mv AT sihuichen comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments
AT sihuichen comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments
AT yijiang comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments
AT yijiang comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments
AT guoqinxie comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments
AT guoqinxie comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments
AT pengwu comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments
AT pengwu comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments
AT jinyuzhu comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments
AT jinyuzhu comprehensiveanalysisofferroptosisrelatedgenesrevealspotentialtherapeutictargetsinosteoporosispatientsacomputationalanalysisandinvitroexperiments