miR‐125a/b inhibits tumor‐associated macrophages mediated in cancer stem cells of hepatocellular carcinoma by targeting CD90

Abstract

Cancer stem cells promote tumorigenesis and progression of hepatocellular carcinoma (HCC). Recently, emerging evidence indicates tumor-associated macrophages (TAMs) play an important role in tumor progression. However, TAMs often occurs with unknown mechanisms. As an important mediator in intercellular communications, exosomes secreted by host cells mediate the exchange of genetic materials and proteins, which involves tumor aggressiveness.The aim of the study was to investigate whether exosomes derived from TAMs mediate stem cell properties in HCC. TAMs were isolated from the tissues of HCC. microRNA (miRNA) expression profiles of TAMs were analyzed using miRNA microarray. In vitro cell coculture was further conducted to investigate the crosstalk between TAMs and tumor cells mediated by TAMs exosomes. In this study, we showed that TAMs exosomes promote HCC cell proliferation and stem cell properties. Using miRNA profiles assay, we identified significantly lower levels of miR-125a and miR-125b in exosomes and cell lysate isolated from TAMs.Functional studies revealed that the HCC cells were treated with TAM exosomes or transfected with miR-125a/b suppressed cell proliferation and stem cell properties by targeting CD90, a stem cell marker of HCC stem cells. The study indicated that miR-125a/b targeting CD90 played important roles in cancer stem cells of HCC. K E Y W O R D S cancer stem cell (CSC), CD90, hepatocellular carcinoma (HCC), macrophages, miR-125a, miR-125b J Cell Biochem. 2019;120:3046-3055. wileyonlinelibrary.com/journal/jcb How to cite this article: Wang Y, Wang B, Xiao S, Li Y, Chen Q. miR-125a/b inhibits tumorassociated macrophages mediated in cancer stem cells of hepatocellular carcinoma by targeting CD90. J Cell Biochem. 2019;120:3046-3055.

MicroRNAs in tumor immunity: functional regulation in tumor-associated macrophages

“…Downregulation of BRG1, in turn, promotes colon cancer metastasis through activating the Wnt/β-catenin pathway (Lan et al, 2019). Using a HCC cell line, Wang et al (2019) found that miR-125a and miR-125b were downregulated in exosomes from TAMs, and transfection of miR-125a/125b effectively suppressed the proliferation and migration of HCC cells via downregulation of CD90.…”

MicroRNAs: As Critical Regulators of Tumor- Associated Macrophages

“…MiR-21-5p also creates an immunosuppressive environment in epithelial ovarian carcinoma [ 104 ]. In HCC, exosomal miR125a/b released from TAMs in the TME negatively influences tumor cell division and stemness properties by targeting CD90 [ 106 ]. Wang et al suggested that exosomes containing miR-125a/b could be potential therapeutic targets to design next-generation therapeutics for HCC patients [ 106 ].…”

“…In HCC, exosomal miR125a/b released from TAMs in the TME negatively influences tumor cell division and stemness properties by targeting CD90 [ 106 ]. Wang et al suggested that exosomes containing miR-125a/b could be potential therapeutic targets to design next-generation therapeutics for HCC patients [ 106 ]. Whereas, exosomal-miR-21 secreted from M2-like macrophages imparts chemoresistance in gastric cancer cells by modulating the PI3K/Akt axis [ 107 ].…”

Advances in surface markers of liver cancer stem cell

“…Gene expression analysis shows that EpCAM+ cells display epithelial characteristics, while CD90+ cells exhibit a vascular endothelial type of gene profile [95] . Exosomes containing miR-125a and miR-125b derived from TAMs mediate stem cell properties in HCC by targeting CD90 [96] . Zhang et al [97] demonstrated that has 0067531 affected the biological functions of CD90+ HCC cells by regulating P13K-AKT signaling pathway.…”