MicroRNAs and polymorphisms influencing MICA immune modulation

MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in post-transcriptional gene regulation. They act mainly by interacting with sequences located in the 3' untranslated regions (3'UTRs) of messenger RNAs (mRNAs), thereby influencing mRNA stability and translation. Through these mechanisms, miRNAs contribute to the fine-tuning of multiple biological pathways, including immune activation, inflammatory signaling, and cellular stress responses. Among the genes involved in immune surveillance, the major histocompatibility complex class I polypeptide-related sequence A (MICA) has emerged as an important target for post-transcriptional regulation due to its role as a ligand for the activating receptor NKG2D (natural killer cell group 2-D), which is expressed in natural killer (NK) cells and cytotoxic T lymphocytes. MICA is highly polymorphic, and several allelic variants differ in sequence composition, structural organization, and expression patterns, potentially influencing miRNA-mRNA interactions. Growing evidence suggests that miRNA-mediated regulation of MICA contributes to immune modulation in cancer, viral infections, and autoimmune disorders, particularly through mechanisms associated with immune evasion and altered NKG2D signaling. In addition, genetic polymorphisms and structural variations within regulatory regions, especially within the 3'UTR, can alter miRNA binding affinity by creating, disrupting, or modifying target sites. This mini review discusses the current understanding of miRNA-mediated regulation of MICA, emphasizing the impact of allelic diversity and regulatory polymorphisms on post-transcriptional control. Furthermore, it highlights current knowledge gaps and future perspectives regarding allele-specific regulation.