microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway

Nanoscale Research Letters

Chang She¹  Xiaowen Deng²  Ya Peng²  Xiangsheng Li²  Huowang Liu³  An Liu³  Chenxi Liu⁴  Xinxing Wang⁴ 

[1]5th Department of Cardiology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, 410005, Changsha, Hunan, People’s Republic of China

[2]Department of Otolaryngology Head and Neck Surgery, Affiliated Changsha Hospital of Hunan Normal University, The Fourth Hospital of Changsha, 410006, Changsha, Hunan, People’s Republic of China

[3]Department of Otolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, 410013, Changsha, Hunan, People’s Republic of China

[4]Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, 410013, Changsha, Hunan, People’s Republic of China

关键词: Nasopharyngeal carcinoma;    M2 macrophages;    MicroRNA-18a;    Transforming growth factor-beta III receptor;    Transforming growth factor signaling pathway;    Viability;    Apoptosis;    Migration;    Invasion;   

DOI  :  10.1186/s11671-020-03416-8

来源: Springer

【 摘 要 】

ObjectivesNasopharyngeal 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.MethodsPeripheral 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.ResultsMiR-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.ConclusionOur 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.

【 授权许可】

CC BY