Objectives

Nasopharyngeal carcinoma (NPC) is a type of nasopharyngeal disease with high metastasis and invasion properties. Tumor-associated alternative activated (M2) macrophages are evidenced to connect with NPC. Based on this, this study purposes to explore the mechanism and participation of microRNA-18a (miR-18a) from M2 macrophages in NPC.

Methods

Peripheral blood mononuclear cells were differentiated to macrophages and macrophages were polarized to M2 type by interleukin-4. SUNE-1 and CNE2 cells were transfected with restored or depleted miR-18a or transforming growth factor-beta III receptor (TGFBR3) to explore their roles in NPC progression with the involvement of the TGF-β signaling pathway. Next, SUNE-1 and CNE2 cells were co-cultured with M2 macrophages that had been treated with restored or depleted miR-18a or TGFBR3 to comprehend their combined roles in NPC with the involvement of the TGF-β signaling pathway.

Results

MiR-18a was highly expressed and TGFBR3 was lowly expressed in NPC cells. MiR-18a restoration, TGFBR3 knockdown or co-culture with miR-18a mimics, or si-TGFBR3-transfected M2 macrophages promoted SUNE-1 cell progression, tumor growth in mice, decreased p-Smad1/t-Smad1, and elevated p-Smad3/t-Smad3. miR-18a downregulation, TGFBR3 overexpression, or co-culture with miR-18a inhibitors or OE-TGFBR3-transfected M2 macrophages depressed CNE2 cell progression, tumor growth in mice, increased p-Smad1/t-Smad1, and decreased p-Smad3/t-Smad3.

Conclusion

Our study elucidates that miR-18a from M2 macrophages results in promoted NPC cell progression and tumor growth in nude mice via TGFBR3 repression, along with the Smad1 inactivation and Smad3 activation.

中文翻译：

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M2 巨噬细胞的 microRNA-18a 通过 TGF-β 信号通路抑制 TGFBR3 促进鼻咽癌进展和肿瘤生长

 目标

鼻咽癌（NPC）是一种具有高转移性和侵袭性的鼻咽疾病。肿瘤相关替代激活 (M2) 巨噬细胞已被证明与 NPC 相关。基于此，本研究旨在探讨来自M2型巨噬细胞的微小RNA-18a（miR-18a）在鼻咽癌中的作用机制和参与。

 方法

外周血单核细胞分化为巨噬细胞，巨噬细胞被白细胞介素4极化为M2型。 SUNE-1 和 CNE2 细胞用恢复或耗尽的 miR-18a 或转化生长因子-β III 受体 (TGFBR3) 转染，以探索它们在 TGF-β 信号通路参与的 NPC 进展中的作用。接下来，将 SUNE-1 和 CNE2 细胞与经过恢复或耗尽的 miR-18a 或 TGFBR3 处理的 M2 巨噬细胞共培养，以了解它们在 NPC 中涉及 TGF-β 信号通路的联合作用。

 结果

鼻咽癌细胞中miR-18a高表达，TGFBR3低表达。 MiR-18a 恢复、TGFBR3 敲低或与 miR-18a 模拟物共培养或 si-TGFBR3 转染的 M2 巨噬细胞促进 SUNE-1 细胞进展、小鼠肿瘤生长、p-Smad1/t-Smad1 降低和 p-Smad1 升高Smad3/t-Smad3。 miR-18a 下调、TGFBR3 过表达或与 miR-18a 抑制剂或 OE-TGFBR3 转染的 M2 巨噬细胞共培养可抑制 CNE2 细胞进展、小鼠肿瘤生长、p-Smad1/t-Smad1 增加和 p-Smad3/ 减少t-Smad3。

 结论

我们的研究阐明，来自 M2 巨噬细胞的 miR-18a 通过 TGFBR3 抑制以及 Smad1 失活和 Smad3 激活，促进裸鼠中的 NPC 细胞进展和肿瘤生长。