Morphine contributed to the deterioration of cancer via miR-543/MARCKS/FcγR-mediated phagocytosis pathway.

It has been confirmed that morphine was detrimental to patients with cancers. Hence, we aimed to reveal a certain mechanism of morphine in cancer development.Microarray and GSEA analysis were utilized to seek for differently expressed genes and pathway.

Bioinformatics analysis identified that downregulation of MARCKS and upregulation of miR-543 in samples treated with morphine. FcγR-mediated phagocytosis pathway was illustrated to be upregulated in the control. PANC-1 and DU145 cell viability was increased but apoptosis was declined as morphine concentration went up from 10^-8 to 10^-6 mol/l. On the other curve, the viability was reduced and apoptosis was elevated from 10^-6 to 10^-5 mol/l. The expression of miR-543 ran the same trend as cell viability. Assays in vivo and in vitro validated that miR-543 facilitated cell viability, tumour growth, levels of CA199 and PSA, whereas inhibited apoptosis. MARCKS could target and inhibit miR-543 expression, which exhibited an opposite effect on cancer progression. MiR-543 blocked but MARCKS activated FcγR-mediated phagocytosis pathway.

Morphine at 10^-6 mol/l could benefit miR-543 expression to inhibit MARCKS expression, consequently, blocking FcγR-mediated phagocytosis pathway, which contributed to the cancer progression in vitro and in vivo.