LncRNA GAS5 Inhibits Progression of Colorectal Cancer by Regulating M1/M2 Macrophages Polarization

摘要

Macrophages are highly malleable and can dynamically switch between the Ml and M2 polarization phenotypes. We investigated the role of long non-coding RNA GAS5 in the regulation of macrophage polarization in colorectal cancer. LPS+IFNy and IL-4 were used to induce macrophage differentiation into Ml and M2, respectively. We selected human colorectal cancer cell line SW480 to be co-incubated with Ml or M2 macrophages. Real-time quantitative PCR was used to detect the expression of lncRNA GAS5 and macrophage-associated mRNA. ELISA was used to detect IL-1β, TNFa, IL-12 and IL-10 expression. Cck8 assay, colony formation assay and flow cytometry were used to detect the biological function of colorectal cancer cells. Ml type macrophages have higher expression of IncRNA GAS5 than M2 type macrophages. Downregulation of lncRNA GAS5 caused reduction of cytokines expression (IL-12, iNOS, IL-1β and TNF-a) in Ml macrophages and increase of cytokines IL-10, TGFβ, Arg-1 and Fizz-1 expression level in M2 macrophages (P<0.05). Tumor-suppressive functions of Ml macrophages on CRC were weaken and tumor-promoting functions of M2 macrophages on CRC were enhanced while knocking down GAS5. These findings indicate that IncRNA GAS5 inhibits colorectal cancer cell immune escape and tumor growth by promoting polarization of Ml macrophages.