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Long non‐coding RNA cox‐2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization
Author(s) -
Ye Yibiao,
Xu Yunxiuxiu,
Lai Yu,
He Wenguang,
Li Yanshan,
Wang Ruomei,
Luo Xinxi,
Chen Rufu,
Chen Tao
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26509
Subject(s) - macrophage polarization , cancer research , flow cytometry , m2 macrophage , cell growth , small interfering rna , biology , vimentin , cell , cell culture , macrophage , chemistry , microbiology and biotechnology , immunology , transfection , in vitro , immunohistochemistry , biochemistry , genetics
Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. We investigate long non‐coding RNA (lncRNA) cox‐2 in macrophage polarization and the regulatory mechanism functions in hepatocellular carcinoma (HCC). Lipopolysaccharide (LPS) was used to induce RAW264.7 macrophages into M1 type, and IL‐4 was to induce RAW264.7 macrophages into M2 type. We selected mouse hepatic cell line Hepal‐6 and hepatoma cell line HepG2 for co‐incubation with M1 or M2 macrophages. Quantitative real‐time PCR was used to detect the expressions of lncRNA cox‐2 and mRNAs. ELISA was conducted for testing IL‐12 and IL‐10 expressions; Western blotting for epithelial mesenchymal transition related factors (E‐cadherin and Vimentin). An MTT, colony formation assay, flow cytometry, transwell assay, and stretch test were conducted to test cell abilities. The M1 macrophages had higher lncRNA cox‐2 expression than that in the non‐polarized macrophages and M2 macrophages. The lncRNA cox‐2 siRNA decreased the expression levels of IL‐12, iNOS, and TNF‐α in M1 macrophages, increased the expression levels of IL‐10, Arg‐1, and Fizz‐1 in M2 macrophages (all P < 0.05). The lncRNA cox‐2 siRNA reduces the ability of M1 macrophages to inhibit HCC cell proliferation, invasion, migration, EMT, angiogenesis and facilitate apoptosis while strengthening the ability of M2 macrophages to promote proliferation HCC cell growth and inhibit apoptosis. These findings indicate that lncRNA cox‐2 inhibits HCC immune evasion and tumor growth by inhibiting the polarization of M2 macrophages.