Abstract
Nasopharyngeal carcinoma (NPC) causes severe oncogenic lesions in the nasopharynx. CD47, a transmembrane integrin-associated protein, plays a key role in the ability of tumor cells to escape phagocytosis, working as an immune checkpoint in the immune response. Besides this role, CD47 has been reported to regulate cell proliferation and migration. The present study addresses the relationship between CD47 and microRNA-200a and examines their regulatory mechanisms in NPC. Bioinformatics analyses and dual-luciferase reporter assays were used to confirm the putative relationship between miR-200a and CD47, and their interaction was further detected using western blotting and RT-PCR. Further, results showed that miR-200a affect NPC cell proliferation, migration, and invasion by regulating CD47. A cell phagocytosis assay showed that miR-200a and a CD47 monoclonal antibody increased the sensitivity of NPC cells to macrophage phagocytosis by inhibiting the functions of CD47. Additionally, miR-200a expression was suppressed and CD47 expression increased in both clinical NPC tissues and cell lines. Taken together, these results show the miR-200a/CD47 combination as a potential therapeutic for treatment of NPC.
Highlights
Nasopharyngeal carcinoma (NPC) affects the nasopharynx and varies in prevalence by geographic region and ethnicity [1]
The results show that impairments in migration and invasion observed in NPC cells as a result of CD47 suppression were rescued by the miR-200a inhibitor (Figure 4)
Anti-CD47 antibody administration resulted in a dramatically higher proportion of NPC cells phagocytosed by macrophages than did treatment with control IgG, confirming that CD47 plays a key role in tumor cell escape from immune surveillance [29, 30]
Summary
Nasopharyngeal carcinoma (NPC) affects the nasopharynx and varies in prevalence by geographic region and ethnicity [1]. It has been reported that CD47 expression in multiple tumors is regulated by microRNAs (miRNAs) including miR-133a, miR-155, and miR-708 [16,17,18]. A recent study demonstrated a potential interaction between miR-200a and PD-L1, showing that miR-200 family members inhibit PD-1 signaling by targeting PD-L1 to prevent tumors from escaping immune surveillance [22]. Based on recent reports that miRNAs efficiently regulate immune responses as modulators of immune checkpoint molecules and their potential as cancer therapeutic targets and agents [17, 23, 24], it is reasonable to speculate that miRNAs could affect CD47 and exert associated effects on immune checkpoints during NPC tumorigenesis
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