Unconventional microRNA role: Enhancing the human leukocyte antigen class I antigen processing pathway via interacting with a silencer

Abstract

This study reports an unconventional, silencer-interacting role of miR‑155‑5p in tumor cells. By binding a repressive site within the tapasin (TAPBP) 3′UTR, miR‑155‑5p weakens silencer activity, increasing tapasin levels, stabilizing peptide loading of HLA‑I, and boosting HLA‑I surface expression. CRISPR edits, luciferase reporters, qPCR/Western blots, and flow cytometry support the mechanism; analyses of public melanoma cohorts relate miR‑155/TPN status to immune infiltration and outcome. Functionally, higher HLA‑I correlates with reduced NK degranulation toward target cells, consistent with restored antigen presentation and altered immune interactions.