{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T13:06:48Z","timestamp":1779973608880,"version":"3.53.1"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myocardial fibrosis is a common pathological feature of multiple cardiovascular diseases, including heart failure, hypertension, and myocardial infarction, and is associated with poor prognosis. Despite extensive research, clinically validated molecular biomarkers for early diagnosis and reliable therapeutic targets for myocardial fibrosis remain limited. Post-translational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, SUMOylation, and glycosylation, are critical regulators of fibrosis-related signaling pathways, yet a systematic bioinformatics-driven identification of PTM-related hub genes has not been performed. Three publicly available GEO datasets (GSE57345, GSE133054, GSE76314) comprising cardiac tissue from heart failure and control patients were integrated. Differentially expressed genes (DEGs) were identified using the limma package, then intersected with a curated PTM gene set derived from PhosphoSitePlus and UniProt databases. Weighted gene co-expression network analysis (WGCNA) identified fibrosis-associated modules, and protein\u2013protein interaction (PPI) network analysis via STRING and CytoHubba pinpointed hub genes. Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis across independent validation cohorts. Immune cell infiltration was estimated using CIBERSORT.Molecular docking with AutoDock Vina (version 1.2.3) was performed to evaluate binding affinity of FDA-approved cardiovascular drugs against identified hub protein targets. A total of 863 DEGs were identified in the training cohort (|log2FC| &gt; 1.0, adjusted p &lt; 0.05), of which 138 overlapped with the PTM gene set. WGCNA revealed a turquoise module (r = 0.79, p &lt; 0.001) most significantly correlated with fibrosis severity. PPI analysis identified five hub genes: SIRT3, SMAD3, NEDD4L, UBC9, and CAMK2D. ROC analysis demonstrated strong diagnostic performance (AUC range: 0.82\u20130.92) validated in independent cohorts. Hub genes showed significant correlations with M2 macrophage infiltration. Molecular docking identified spironolactone and finerenone as top-ranked ligands with binding energies of \u22128.7 and \u22128.4 kcal\/mol against SMAD3 and SIRT3, respectively. This study, which is entirely in silico and based on publicly available transcriptomic datasets, systematically identifies five PTM-related hub genes as candidate diagnostic biomarkers and prioritised drug-repurposing targets in myocardial fibrosis. These findings are hypothesis-generating and require experimental validation (protein-level confirmation, cell- and animal-based functional assays, and biophysical binding studies) before any diagnostic or therapeutic claim can be made.<\/jats:p>","DOI":"10.3390\/ijms27114877","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:09:07Z","timestamp":1779970147000},"page":"4877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioinformatics Identification and Molecular Docking Validation of Post-Translational Modification-Related Hub Genes as Diagnostic Biomarkers and Therapeutic Targets in Myocardial Fibrosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2363-6024","authenticated-orcid":false,"given":"Xueqin","family":"Yu","sequence":"first","affiliation":[{"name":"Medical School of Tianjin University, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Du","sequence":"additional","affiliation":[{"name":"Medical School of Tianjin University, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxing","family":"Zuo","sequence":"additional","affiliation":[{"name":"Medical School of Tianjin University, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical School of Tianjin University, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e10865","DOI":"10.15252\/emmm.201910865","article-title":"Targeting cardiac fibrosis in heart failure with preserved ejection fraction: Mirage or miracle?","volume":"12","author":"Sweeney","year":"2020","journal-title":"EMBO Mol. 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