# LncRNAs at the Crossroads of Precision Nutrition and Cancer Chemoprevention

## TL;DR

This review explores how long non-coding RNAs (lncRNAs) connect diet to cancer prevention, offering new ways to personalize nutrition for cancer risk reduction.

## Contribution

The paper introduces lncRNAs as a molecular bridge linking dietary bioactives to cancer prevention, proposing AI-driven frameworks for precision nutrition strategies.

## Key findings

- Dietary bioactives like curcumin, resveratrol, and omega-3 fatty acids modulate lncRNAs with tumor-suppressive or oncogenic roles.
- lncRNA signatures reflect nutritional states and could serve as biomarkers for personalized dietary interventions.
- Systems biology and AI can map nutrient–lncRNA interactions to identify targets for cancer chemoprevention.

## Abstract

Nutrition shapes many of the biological pathways involved in cancer, yet people often respond very differently to the same foods or dietary supplements. Long non-coding RNAs have emerged as important regulatory molecules that influence gene expression, cellular metabolism, inflammation, and stress response—processes central to cancer development. Growing evidence indicates that these RNAs are very sensitive to dietary bioactive compounds, positioning them as a critical molecular interface between nutrition and cancer biology. In this review, we explore how natural bioactive substances, vitamins, minerals, and fatty acids modulate long non-coding RNAs with either oncogenic or tumor-suppressive functions. We also discuss how systems biology approaches and artificial intelligence can be used to map nutrient–RNA interactions and uncover actionable targets for cancer prevention. By integrating nutritional science with molecular and computational frameworks, this review highlights the potential of long non-coding RNAs to inform more personalized and effective dietary strategies for reducing cancer risk.

Cancer remains a leading cause of morbidity and mortality worldwide, and effective strategies for cancer prevention are urgently needed to complement therapeutic advances. While dietary factors are known to influence cancer risk, the molecular mechanisms that mediate inter-individual responses to nutritional exposures remain poorly defined. Emerging evidence identifies long non-coding RNAs (lncRNAs) as pivotal regulators of gene expression, chromatin organization, metabolic homeostasis, immune signaling, and cellular stress responses, the core processes that drive cancer initiation and progression and are highly sensitive to nutritional status. In parallel, advances in precision nutrition have highlighted how variability in genetics, metabolism, microbiome composition, and epigenetic landscapes shape dietary influences on cancer susceptibility. This review integrates these rapidly evolving fields by positioning lncRNAs as molecular conduits that translate dietary exposures into transcriptional and epigenetic programs governing cancer development, progression, and therapeutic vulnerability. We provide mechanistic evidence demonstrating how dietary bioactive compounds and micronutrients, including polyphenols [such as curcumin, resveratrol, epigallocatechin gallate (EGCG)], flavonoids, alkaloids such as berberine, omega-3 (ω-3) fatty acids, folate, vitamin D, probiotic metabolites (such as butyrate and propionate), and trace elements (such as selenium and zinc), modulate oncogenic and tumor-suppressive lncRNAs. These nutrient–lncRNA interactions influence cancer-relevant pathways controlling proliferation, epithelial–mesenchymal transition (EMT), inflammation, oxidative stress, and metabolic rewiring. We further discuss emerging lncRNA signatures that reflect nutritional and metabolic states, their potential utility as biomarkers for individualized dietary interventions, and their integration into liquid biopsy platforms. Leveraging multi-omics datasets and systems biology, we outline AI-driven frameworks to map nutrient–lncRNA regulatory networks and identify targetable nodes for cancer chemoprevention. Finally, we address translational challenges, including compound bioavailability, inter-individual variability, and limited clinical validation, and propose future directions for incorporating lncRNA profiling into precision nutrition-guided cancer prevention trials. Together, these insights position lncRNAs at the nexus of diet and cancer biology and establish a foundation for mechanistically informed precision nutrition strategies in cancer chemoprevention.