Integrative RNA-Seq Analysis Reveals Stress Type-Dependent lncRNA-Centered Co-Expression Networks Across Human Cellular Stress Contexts

Authors

• Christina Anastasiadi
• Aggeliki Kasapi
• Ioannis Sentementes
• Vasileios Gouzouasis
• Margaritis Tsifintaris, Thomas Jefferson UniversityFollow
• Antonis Giannakakis

Document Type

Article

Publication Date

8-15-2026

Comments

This article is the author’s final published version in International Journal of Molecular Sciences, Volume 27, Issue 16, 2026, Article number 7288.

The published version is available at https://doi.org/10.3390/ijms27167288. Copyright © 2026 by the authors.

Abstract

Long non-coding RNAs (lncRNAs) are emerging as important regulators of cellular adaptation to environmental and molecular stress, but the extent to which their responses remain reproducible and stress-type-dependent across human stress conditions remains unclear. Here, we performed an integrative transcriptomic meta-analysis of human stress-response datasets from ASTRA and GEO, focusing on normal, non-cancerous, wild-type human cell lines exposed to oxidative stress (H2O2), hypoxia, heat stress, or UV-induced DNA damage. Gene Ontology (GO) enrichment analysis of differentially expressed (DE) protein-coding mRNAs confirmed that the resulting stress-stratified comparison captured biologically coherent transcriptional programmes to oxidative stress signaling, hypoxic and metabolic adaptation, heat-induced proteostasis, UV-induced DNA damage signaling, apoptosis, and cell-cycle regulation. Differential expression analysis was subsequently integrated with Weighted Gene Co-expression Network Analysis (WGCNA) -based module–treatment associations to rank network-supported lncRNA candidates. By prioritizing candidates for recurrence across at least two different stress studies, we identified lncRNAs with increased recurrence and consistent stress-type-dependent expression regulation, embedded within coordinated stress-associated mRNA programs.

Recommended Citation

Anastasiadi, Christina; Kasapi, Aggeliki; Sentementes, Ioannis; Gouzouasis, Vasileios; Tsifintaris, Margaritis; and Giannakakis, Antonis, "Integrative RNA-Seq Analysis Reveals Stress Type-Dependent lncRNA-Centered Co-Expression Networks Across Human Cellular Stress Contexts" (2026). Computational Medicine Center Faculty Papers. Paper 70.
https://jdc.jefferson.edu/tjucompmedctrfp/70

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

42653292

Language

English