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.