MiR-146b Regulates TAMs To Affect The Growth Of Subcutaneous Tumor Of Mouse Colon Cancer Cells And The Therapeutic Effect Of PD-1/PD-L1 Blocking Therapy

Colon cancer is one of the most common malignant tumors.Its incidence rate and mortality rate are increasing year by year.MicroRNA,as an important regulator of life process,is closely related to genetic diseases such as tumor.In order to explore the effect of miR-146 on the growth of subcutaneous tumor of colon cancer cells in mice,we established two animal models.Compared with WT mice,the growth of MC38 cell subcutaneous tumor in miR-146b-/-mice was promoted.The MC38 cell subcutaneous tumor model of C57BL/6 mice treated with mimic showed that the growth of MC38 cell subcutaneous tumor of miR-146b-/-mice was inhibited after the treatment with mimic.Tumor associated macrophages(TAMs)are the most abundant type of immune cells infiltrating into tumor tissues.Their infiltration and phenotypic changes,especially M2 polarization,are closely related to tumor progression and progression.It is suggested that miRNA may mediate the downstream target genes in tumor cells or indirectly act on tumor cells by influencing the polarization process of macrophages.Our previous study found that miR-146b plays an important role in the regulation of M1 macrophage activation.In order to investigate the effect of miR-146b on the phenotype and function of tumor related macrophages,we first conducted a series of in vitro experiments.The results of TAMs flow cytometry in the subcutaneous tumor tissue of C57BL/6 mice with miR-146b-/-and WT showed that miR-146b-/-upregulated the TAMs of M2 phenotype in tumor microenvironment,the results of flow cytometry and Q-PCR showed that miR-146b-/-promoted M2 polarization of BMDMs.The results of Transwell migration experiment showed that the M2 macrophages of miR-146b-/-promoted tumor cell migration.In vivo,the MC38 cell subcutaneous tumor model of C57BL/6 mice with macrophage deficiency showed that miR-146b-/-promoted the growth of subcutaneous tumor by regulating macrophages.The results of C57BL/6 mice model of subcutaneous tumor by mixed injection of allogeneic macrophages and MC38 tumor cells showed that M2 macrophages from miR-146b-/-could promote the growth of subcutaneous tumor.The results of these two models indicate that miR-146b-/-promotes the growth of subcutaneous tumor by regulating TAMs.