Article

Non-coding RNAs at the intersection of interferon signaling and cancer: mechanistic insights and clinical prospects

Usamah SayedFaculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan. Electronic address: [email protected]Waleed K. AbdulsahibDepartment of Pharmacology and Toxicology, College of Pharmacy, Al Farahidi University, Baghdad, Iraq. Electronic address: [email protected]S. Renuka JyothiDepartment of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India. Electronic address: [email protected]Priya Priyadarshini NayakDepartment of Medical Oncology, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha 751003, India. Electronic address: [email protected]Ashish Singh ChauhanUttaranchal Institute of Pharmaceutical Sciences, Division of research and innovation, Uttaranchal University, Dehradun, Uttarakhand, India. Electronic address: [email protected]Siya SinglaCentre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura 140401, Punjab, India. Electronic address: [email protected]D. PolatovaScientific-Practical Medical Center for Pediatric Oncology, Hematology and Immunology, Tashkent, Uzbekistan. Electronic address: [email protected]Fadhil Faez SeadDepartment of Dentistry, College of Dentistry, The Islamic University, Najaf, Iraq; Department of medical analysis, Medical laboratory technique college, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq. Electronic address: [email protected]Reza Akhavan-SigariDr. Schneiderhan GmbH and ISAR Klinikum Munich, Germany; Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Poland. Electronic address: [email protected]

Cancer Treatment and Research Communicationsjournal2026en

ABI

Abstract

Interferon (IFN) signaling plays a vital role in influencing tumor outcomes, acting as a switch between immune control and evasion based on the situation. When IFN responses are acute and well-regulated, they enhance processes such as antigen processing, dendritic cell activation, cytotoxic lymphocyte response, and the activation of interferon-stimulated genes (ISGs), which lead to cell cycle arrest and programmed cell death. Conversely, prolonged or dysfunctional IFN signaling can be exploited by tumors, resulting in immunoediting, increased checkpoint molecule expression, T-cell exhaustion, stress tolerance, and resistance to therapy and metastasis. The tumor microenvironment (TME) affects this dual role by influencing immune cell infiltration, stromal and blood vessel behavior, and metabolic constraints. Non-coding RNAs (ncRNAs)-including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)-add an extra regulatory layer by modulating IFN induction, JAK-STAT signaling, IRF/STAT-driven gene transcription, and ISG programming. There exists a bidirectional relationship: tumor-suppressive ncRNAs enhance IFN responses and immunogenicity, whereas oncogenic ncRNAs can suppress signaling and facilitate immune escape. The discussion also explores compartment-specific effects within the TME, links to epithelial-mesenchymal transition (EMT) and metastatic plasticity, and the potential of ncRNAs as biomarkers, therapeutic targets, and the challenges in translating these insights into clinical practice.

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Identifiers

DOI: 10.1016/j.ctarc.2026.101155

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