Abstract
MicroRNAs (miRNAs) play an important role in regulating gene expression and immune responses. Of interest, miR-181a and miR-146a are key players in regulating immune responses and are among the most abundant miRNAs expressed in NK cells. Bioinformatically, we predicted miR-181a to regulate the expression of the natural cytotoxicity receptor NCR2 by seeded interaction with the 3'-untranslated region (3'-UTR). Whereas, miR-146a expression was not significantly different (P = 0.7361), miR-181a expression was, on average 10-fold lower in NK cells from breast cancer patients compared to normal subjects; P < 0.0001. Surface expression of NCR2 was detected in NK cells from breast cancer patients (P = 0.0384). While cytokine receptor-induced NK cell activation triggered overexpression of miR-146a when stimulated with IL-2 (P = 0.0039), IL-15 (P = 0.0078), and IL-12/IL-18 (P = 0.0072), expression of miR-181a was not affected. Overexpression or knockdown of miR-181a or miR-146a in primary cultured human NK cells did not affect the level of expression of any of the three NCRs; NCR1, NCR2 or NCR3 or NK cell cytotoxicity. Expression of miR-181a and miR-146a did not correlate to the expression of the NCRs in NK cells from breast cancer patients or cytokine-stimulated NK cells from healthy subjects.