Integrative Biomedical Research
Integrative Biomedical Research (Journal of Angiotherapy) | Online ISSN 3068-6326
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Volume 10 Number 1 2026
REVIEWS (Open Access)
Non-Coding RNA Networks in Pancreatic Ductal Adenocarcinoma: An Expanding Regulatory Landscape from the ceRNA TRIAD to Exosomal Immune Evasion and Ferroptosis Escape
Siti Fathiah Masre1,*, Eng Wee Chua2, Muhammad Asyaari Zakaria1, Amnani Aminuddin2, Nor Fadilah Rajab3
Integrative Biomedical Research 10 (1) 1-8 https://doi.org/10.25163/biomedical.10110921
Submitted: 19 January 2026 Revised: 07 March 2026 Accepted: 15 March 2026 Published: 17 March 2026
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains, even now, one of the few cancers where survival curves have barely moved in a generation, and that persistence is what motivated this review. Decades of work mapping driver mutations in KRAS, TP53, CDKN2A, and SMAD4 have not, on their own, translated into durable clinical benefit, which has pushed the field toward a broader, network-level view of the roughly 98% of the transcribed genome that never becomes protein — the non-coding RNAs (ncRNAs). we conducted a structured narrative synthesis of the peer-reviewed literature on lncRNAs, circular RNAs (circRNAs), microRNAs (miRNAs), and tRNA-derived small RNAs (tsRNAs) in PDAC, searching PubMed, Scopus, and Web of Science for studies published through 2026 and organizing the retrieved evidence around mechanistic themes rather than chronology, The evidence converges on an integrated lncRNA-miRNA-mRNA "TRIAD," in which oncogenic transcripts such as PVT1, UCA1, and MALAT1 sponge tumor-suppressive miRNAs while lncRNAs like GAS5 and MEG3 normally hold this network in check. Circular RNAs add a further, more stable layer — most strikingly exosomal circGANAB, which does not simply sponge miRNAs but physically degrades protective lncRNAs and cytokine transcripts, thereby upregulating GPX4-driven ferroptosis resistance and excluding cytotoxic T cells from the tumor core. Metabolic circuits (glutathione and riboflavin pathways) and stable serum tsRNA panels emerged as both mechanistic drivers and promising, minimally invasive biomarkers, while natural phytochemicals such as cordycepin and curcumin showed consistent, if pharmacokinetically limited, potential to re-sensitize resistant cells. Rather than isolated lesions, these ncRNA circuits behave as a coordinated regulatory system that shapes PDAC identity, stromal crosstalk, and therapeutic escape, and disrupting specific nodes within it — particularly the exosomal circGANAB axis — may offer a genuinely new route toward diagnosis and multi-target therapy in a disease that has resisted almost everything else.
Keywords: pancreatic ductal adenocarcinoma; non-coding RNA; competing endogenous RNA; circular RNA; exosomes; ferroptosis; tumor microenvironment.
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