EZH2 (enhancer of zeste homolog 2) regulates epigenetic gene silencing and functions as critical regulators in various tumor progression. Macrophages infiltration promotes cancer development via stimulating tumor cell migration and invasion. However, the effect of EZH2 on macrophages infiltration, cell invasion, and migration of lung cancer remains to be investigated. In this study, we found that knockdown of EZH2 inhibited macrophages chemotaxis and decreased chemokine ligand 5 (CCL5). Wound‐healing and transwell assays results showed that migration and invasion of lung cancer cells was inhibited by EZH2 deletion. Moreover, EZH2 overexpression increased CCL5 expression. Loss‐of functional assay indicated that the promotion ability of EZH2 on macrophages chemotaxis was inhibited by CCL5 knockdown. Mechanistically, the promotion ability of EZH2 on cell migration and invasion of lung cancer was also inhibited by CCL5 knockdown. The in vivo subcutaneous xenotransplanted tumor model also revealed that silence of EZH2 suppressed lung cancer metastasis and macrophages infiltration via regulation of CCL5. In conclusion, our findings indicated that EZH2 promoted lung cancer metastasis and macrophages infiltration via upregulation of CCL5, which might be the underlying mechanism of EZH2‐induced lung cancer cell progression.

中文翻译：

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EZH2增强CCL5的表达，促进巨噬细胞的募集和肺癌的侵袭。

EZH2（zeste同源物2的增强剂）调节表观遗传基因沉默，并在各种肿瘤进展中起关键调节剂的作用。巨噬细胞浸润通过刺激肿瘤细胞迁移和侵袭促进癌症的发展。但是，EZH2对巨噬细胞浸润，细胞侵袭和肺癌迁移的影响仍有待研究。在这项研究中，我们发现敲低EZH2抑制巨噬细胞趋化性并降低趋化因子配体5（CCL5）。伤口愈合和transwell分析结果表明，EZH2缺失抑制了肺癌细胞的迁移和侵袭。此外，EZH2过表达增加了CCL5表达。功能丧失实验表明，EZH2对巨噬细胞趋化性的促进能力受到CCL5抑制的抑制。从机理上讲，CZH5敲低也抑制了EZH2对肺癌细胞迁移和侵袭的促进能力。的体内皮下异种移植肿瘤模型中也揭示了这种沉默EZH2经由CCL5的调控抑制肺癌转移和巨噬细胞浸润。总之，我们的发现表明EZH2通过上调CCL5促进肺癌转移和巨噬细胞浸润，这可能是EZH2诱导的肺癌细胞进程的潜在机制。