Exosomal lncRNA FENDRR Orchestrates Immune Remodelling and Ferroptosis in the Comorbidity of Lung Cancer and Type 1 Myocardial Infarction

Sep 22, 2026

Lung cancer and Type 1 myocardial infarction increasingly co-occur, yet their molecular interaction remains unclear. This research integrates multi-omics profiling, in vivo/in vitro models, and human clinical samples to define how exosomal long noncoding RNA FENDRR regulates cancer–cardiovascular comorbidity. FENDRR is elevated in thrombus-derived exosomes from T1MI patients and drives cardiomyocyte ferroptosis and ferritinophagy via the NCOA4–GPX4–P62 axis, worsening myocardial injury. FENDRR knockdown reduces cardiac damage in a T1MI rat model and links to immune microenvironment remodelling with prognostic relevance in lung adenocarcinoma.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages34

Reading Time1 h 26 min

AccessFree to download

Introduction

Acute myocardial infarction and comorbidity

Exosomes and exosomal lncRNAs

Wiley Human Mutation Volume 2026, Article ID 8861747, 34 pages [https://doi.org/10.1155/humu/8861747](https://doi.org/10.1155/humu/8861747) Research Article Exosomal lncRNA FENDRR Orchestrates Immune Remodelling and Ferroptosis in the Comorbidity of Lung Cancer and Type 1 Myocardial Infarction Youfu He , 1,2,3 Yu Qian ,4 Zhiwei Zheng , 1,3 Yu Zhou , 1,3 Chen Li ,5 and Qiang Wu 1,3 1Department of Cardiology, Guizhou Provincial People's Hospital, Guiyang City, Guizhou Province, China 2Medical College, Guizhou University, Guiyang City, Guizhou Province, China 3Department of Cardiology, Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases, Guiyang City, Guizhou Province, China 4Department of Cardiology, The Second Aﬃliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, China 5Department of Pharmacy, The First Aﬃliated Hospital of Guangxi Medical University, Nanning City, Guangxi Province, China Correspondence should be addressed to Youfu He; heyoufu0912@163.com and Qiang Wu; [gzgywq@126.com](gzgywq@126.com) Received 20 August 2025; Revised 18 November 2025; Accepted 3 December 2025 Guest Editor: Minghua Ren Copyright © 2026 Youfu He et al. Human Mutation published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Lung cancer and Type 1 myocardial infarction (T1MI) increasingly co-occur, yet the molecular basis underlying their interaction remains unclear. In this study, we combined multiomics proﬁling, in vivo and in vitro models and human clinical samples to investigate the regulatory role of the exosomal long noncoding RNA FENDRR in cancer–cardiovascular comorbidity. We found that FENDRR was markedly elevated in thrombus-derived exosomes from T1MI patients and promoted cardiomyocyte ferroptosis and ferritinophagy through the NCOA4–GPX4–P62 axis, thereby exacerbating myocardial injury. Silencing FENDRR signiﬁcantly alleviated cardiac damage in the T1MI rat model. In contrast, FENDRR was consistently downregulated across multiple cancers, particularly lung adenocarcinoma (LUAD) . Higher FENDRR expression was associated with favourable patient survival, and time-dependent ROC analysis demonstrated robust prognostic performance in LUAD (5 − year AUC = 0 990) . Multiomics and immunogenomic analyses further revealed that FENDRR expression correlated with distinct remodelling of the tumour immune microenvironment, including alterations in immune cell inﬁltration, immune activation scores, chemokine and HLA gene expression and antigen-presentation capacity. These ﬁndings were supported by single-cell analyses and by enhanced CD8+ T-cell and Treg inﬁltration in thrombi from patients with LUAD and T1MI. Collectively, our results identify FENDRR as a context-dependent regulator that promotes myocardial injury but may exert tumour-suppressive and immune-modulatory functions in lung cancer. These insights provide a mechanistic framework for cancer–cardiovascular comorbidity and highlight FENDRR as a potential biomarker and therapeutic target across disease contexts. Keywords: exosomes; FENDRR; immune microenvironment; lung cancer; Type 1 myocardial infarction 1. Introduction Acute myocardial infarction (AMI), particularly Type 1 myocardial infarction (T1MI), has long remained the leading cause of cardiovascular mortality worldwide owing to its high incidence and lethality [1] . T1MI primarily results from the rupture of coronary atherosclerotic plaques and subsequent thrombus formation, and it is most commonly observed among elderly individuals and those with multiple chronic diseases [2] . In recent years, with advances in cancer therapy and an ageing population, the phenomenon of comorbidity between cardiovascular disease and malignancy has become increasingly promine

FAQs

What is the main role of exosomal lncRNA FENDRR in T1MI-related myocardial injury?

FENDRR is markedly elevated in thrombus-derived exosomes from T1MI patients and promotes cardiomyocyte ferroptosis and ferritinophagy through the NCOA4–GPX4–P62 axis, exacerbating myocardial injury.

How was the effect of FENDRR tested in disease models?

The study used multiomics profiling, in vivo and in vitro models, and human clinical samples; it also showed that silencing FENDRR significantly alleviated cardiac damage in a T1MI rat model.

What connection does FENDRR have with lung cancer and the tumor immune microenvironment?

FENDRR is consistently downregulated across cancers, particularly lung adenocarcinoma, and higher expression correlates with favourable survival. Multiomics and immunogenomic analyses indicate that FENDRR relates to distinct remodelling of the tumor immune microenvironment, including immune cell infiltration and antigen-presentation capacity.

Sep 22, 2026

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