Mitochondria‑associated small RNAs in breast cancer: An asymmetric evidence landscape from metabolic rewiring to immune selection (Review)

Mitochondria enable breast cancers (Bc) to switch among metabolic, redox and stress-adaptive states, but the associated small-RNA literature often merges molecules with different origins, itineraries and sites of action.The present critical narrative Review separates bona fide nuclear-encoded mitochondrial microRNAs (mitomiRs), candidate mitochondrial miRNAs, mtdNA-derived miRNA-like RNAs, other mitochondrial small RNAs, cytosolic mitochondrial regulators, extracellular RNA cargo and engineered systems.Their reported functions are organized within a 3R Mito-Ecosystem: Rewiring of cell-autonomous metabolism, mitochondrial-origin RNA-dependent growth signaling, organelle quality and ferroptosis competence; directional Relay of RNA cargo or intact mitochondria; and Release of mitochondrial signals and their immune-sensing consequences.LIFT records Localization, Interaction, Function and Translation separately, while context tiers distinguish Bc RNA perturbation from non-RNA enabling biology, cross-system support and hypotheses.A revision-stage PubMed search informed an illustrative mechanistic comparison, with source and selection limits stated explicitly.Rewiring includes directly perturbed metabolic and ferroptotic relationships and reported mitochondrial-origin tiRNA-Met activity.Relay includes causal extracellular RNA effects and organelle-transfer studies.Release includes miR-25/93-dependent NcOA3-cGAS immune sensing, without demonstrated control over mtdNA-release quantity.A causal chain connecting an endogenous mitochondria-resident or mitochondria-derived small RNA, altered release of a defined mitochondrial signal and a lineage-resolved immune outcome remains unestablished in the evaluated material.Ferroptosis provides a testable interface rather than a universally immune-activating endpoint.Target binding was distinguished from functional rescue and propose source-, time-and lineage-resolved experiments and operational immune-activating or suppressive Release states.These criteria require validation and are not patient classifiers or treatment rules.