A Novel Plasma Biomarker hsa_circ_0080018 Drives DLBCL Progression via M2 Polarization of Tumor‐Associated Macrophages

Noncoding RNAs, including circular RNAs (circRNAs), have been demonstrated to play vital roles in tumorigenesis. Uncovering the functions of circRNAs in tumorigenesis and their underlying regulatory mechanisms may suggest new approaches to the development of novel diagnostic and therapeutic strategies for human cancer. Here we report the important role of hsa_circ-0080018 in diffuse large B-cell lymphoma (DLBCL) progression and the potential impact of hsa_circ-0080018 in DLBCL tumorigenesis. Hsa_circ-0080018 was evidently upregulated in newly diagnosed DLBCL patient plasma, and as a reference to classify GCB and non-GCB subtypes. The high expression of hsa_circ-0080018 also appeared in plasma exosome and can transport to tumor microenvironment (TME). In addition, we found that at the molecular level hsa_circ-0080018 acted as a decoy for miR-625-5p and regulated tumor associated macrophage (TAM) polarization by suppressing miR-625-5p that led to IGF-1/IGF-1R pathway activation. The activated IGF-1/IGF-1R pressed macrophage polarizing to M2 and ultimately promoted tumor progression. Our results provided a new potential biomarker in DLBCL plasma that is correlated with cell of origin (COO). The mechanism of circ-0080018 in tumor progression was plasma generated circ-0080018 delivered to TME by exosome and pushed macrophage polarization. Our research may provide a new target for the DLBCL treatment and prognosis in future.