Dataset Information

MiR-98 modulates macrophage polarization and suppresses the effects of tumor-associated macrophages on promoting invasion and epithelial-mesenchymal transition of hepatocellular carcinoma.

ABSTRACT:

Background

Tumor-associated macrophages (TAMs) are generally recognized as a promoter of tumor progression. miR-98 has been shown to suppress the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. Here, we aim to investigate the role of miR-98-mediated macrophage polarization in HCC progression.

Methods

Human blood monocytes were isolated from healthy male donors and incubated with culture medium collected from HepG2 cells for 7 days. The phenotype of the macrophages was detected. The protein expression was detected by Western blot. Levels of cytokines secreted in culture medium were measured using the specific enzyme-linked immunosorbent assay kits. To explore the role of miR-98 in HCC-conditioned TAMs, HCC cells HepG2 and SMMC7721 were cultured with conditioned medium from HCC-conditioned TAMs that had been transfected with miR-98 mimic/inhibitor. Cell proliferation, migration and invasion assays were performed.

Results

HCC-conditioned TAMs possessed M2-like phenotype, including increased protein expression of CD163 and TNF-?^low, IL-1?^low, TGF-?^high and IL-10^high phenotype. HCC-conditioned TAMs also promoted proliferation, migration, invasion and EMT of HepG2 and SMMC7721 cells. Furthermore, miR-98 modulated macrophage polarization from M2 to M1 in HCC-conditioned TAMs, as evidenced by the alteration of M1- or M2-related cytokines. Moreover, miR-98 mimic significantly suppressed the HCC-conditioned TAMs-mediated promotion of cell migration, invasion and EMT in HepG2 and SMMC7721 cells compared with negative control, whereas miR-98 inhibitor exerted reversed effects.

Conclusions

miR-98 may play a vital role in regulating macrophage polarization, thereby suppressing the TAMs-mediated promotion of invasion and EMT in HCC.

SUBMITTER: Li L

PROVIDER: S-EPMC6035433 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

MiR-98 modulates macrophage polarization and suppresses the effects of tumor-associated macrophages on promoting invasion and epithelial-mesenchymal transition of hepatocellular carcinoma.

Li Lei L Sun Pengfei P Zhang Chengsheng C Li Zongchao Z Cui Kai K Zhou Wuyuan W

Cancer cell international 20180706

<h4>Background</h4>Tumor-associated macrophages (TAMs) are generally recognized as a promoter of tumor progression. miR-98 has been shown to suppress the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. Here, we aim to investigate the role of miR-98-mediated macrophage polarization in HCC progression.<h4>Methods</h4>Human blood monocytes were isolated from healthy male donors and incubated with culture medium collected from H ...[more]

PMID: 29989015

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Project description:BACKGROUND:Implant failure remains a major obstacle to successful treatment via TJA. Periprosthetic osteolysis and aseptic loosening are considered as proof of wear debris-induced disruption of local regulatory mechanisms related to excessive bone resorption associated with osteolysis and the damage at the bone-prosthesis interface. Therefore, there is an immediate need to explore strategies for limiting and curing periprosthetic osteolysis and aseptic loosening. METHODS:We analyzed the in vitro cytokine production by primary mouse bone marrow macrophages (BMMs) that were exposed to ultra-high molecular weight polyethylene (UHMWPE) particles and treated with metformin at different concentrations with or without 5-aminoimidazole-4-carboxamide ribonucleoside to activate or inhibit AMPK. A mouse calvarial model was used to examine the in vivo effects of metformin on UHMWPE particle-induced osteolysis. RESULTS:With particles, primary mouse BMMs secreted more pro-inflammatory cytokines tumor necrosis factor-α and interleukin (IL)-6. Treatment with metformin inhibited these variations and promoted the release of cytokine IL-10 with anti-inflammatory capability. In vivo, metformin reduced the production of pro-inflammatory cytokines, osteoclastogenesis, and osteolysis, increasing IL-10 production. Metformin also promoted the polarization of macrophages to an anti-inflammatory phenotype in vivo via AMPK activation. DISCUSSION:A crucial point in limiting and correcting the periprosthetic osteolysis and aseptic loosening is the inhibition of inflammatory factor production and osteoclast activation induced by activated macrophages. The ability of metformin to attenuate osteolysis induced in mouse calvaria by the particles was related to a reduction in osteoclast number and polarization of macrophages to an anti-inflammatory functional phenotype. CONCLUSIONS:Metformin could limit the osteolysis induced by implant debris. Therefore, we hypothesized that metformin could be a potential drug for osteolysis induced by implant debris.

Dataset Information

MiR-98 modulates macrophage polarization and suppresses the effects of tumor-associated macrophages on promoting invasion and epithelial-mesenchymal transition of hepatocellular carcinoma.

Background

Methods

Results

Conclusions

Publications

MiR-98 modulates macrophage polarization and suppresses the effects of tumor-associated macrophages on promoting invasion and epithelial-mesenchymal transition of hepatocellular carcinoma.

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