The underlying molecular mechanisms of the aberrant expression of components of the HLA
class I antigen processing and presentation machinery (APM) in
tumors leading to evasion from T cell-mediated immune surveillance could be due to posttranscriptional regulation mediated by
microRNAs (miRs). So far, some miRs controlling the expression of different APM components have been identified. Using in silico analysis and an miR enrichment protocol in combination with small
RNA sequencing, miR-26b-5p and miR-21-3p were postulated to target the
3' untranslated region (UTR) of the
peptide transporter TAP1, which was confirmed by high free binding energy and dual
luciferase reporter assays. Overexpression of miR-26b-5p and miR-21-3p in
melanoma cells downregulated the
TAP1 protein and reduced expression of HLA class I
cell surface antigens, which could be reverted by miR inhibitors. Moreover, miR-26b-5p overexpression induced a decreased T cell recognition. Furthermore, an inverse expression of miR-26b-5p and miR-21-3p with TAP1 was found in primary
melanoma lesions, which was linked with the frequency of CD8+ T cell infiltration. Thus, miR-26-5p and miR-21-3p are involved in the HLA class I-mediated immune escape and might be used as
biomarkers or therapeutic targets for HLA class Ilow
melanoma cells.