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

OBJECTIVES: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. METHODS:Microarray and GSEA analysis were utilized to seek for differently expressed genes and pathway. KEY FINDINGS: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. CONCLUSIONS: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.

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