Macrophage-Derived Exosomal miR-31-5p Promotes Oral Squamous Cell Carcinoma Tumourigenesis Through the Large Tumor Suppressor 2-Mediated Hippo Signalling Pathway

被引：42

作者：

Yuan, Yi ^{[1
,2
]}

Wang, Zeyu ^{[1
]}

Chen, Mengqi ^{[1
]}

Jing, Yang ^{[1
]}

Shu, Wei ^{[3
]}

Xie, Zhuoying ^{[4
]}

Li, Zhiyang ^{[5
]}

Xu, Juanyong ^{[1
]}

He, Feng ^{[1
]}

Jiao, Pengfei ^{[1
]}

Wang, Jiaqing ^{[1
]}

Xu, Jiamin ^{[1
]}

Xia, Yan ^{[1
]}

Liu, Siyu ^{[1
]}

Du, Hongming ^{[1
]}

Li, Hongwei ^{[1
,2
]}

Dai, Lu ^{[1
]}

Dai, Youjin ^{[6
]}

Zhang, Yaqin ^{[7
,8
]}

机构：

[1] Nanjing Med Univ, Jiangsu Key Lab Oral Dis, Nanjing 210029, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Affiliated Hosp Stomatol, Dept Oral & Maxillofacial Surg, Nanjing 210029, Jiangsu, Peoples R China

[3] Jiangsu Prov Hosp Tradit Chinese Med, Dept Stomatol, Nanjing 210029, Jiangsu, Peoples R China

[4] Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China

[5] Nanjing Univ, Med Sch, Affiliated Drum Tower Hosp, Dept Clin Lab, Nanjing 210008, Jiangsu, Peoples R China

[6] Nanjing Med Univ, Anim Core Facil, Key Lab Model Anim Res, Nanjing 211166, Jiangsu, Peoples R China

[7] Nanjing Med Univ, Dept Biochem & Mol Biol, Key Lab Human Funct Genom Jiangsu Prov, Nanjing 211166, Jiangsu, Peoples R China

[8] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

来源：

JOURNAL OF BIOMEDICAL NANOTECHNOLOGY | 2021年 / 17卷 / 05期

基金：

中国国家自然科学基金;

关键词：

Oral Squamous Cell Carcinoma; Tumor-Associated Macrophages; Exosomes; miR-31-5p; LATS2; Hippo Pathway; DOWN-REGULATION; LATS2; DIVERSITY; GROWTH; PROLIFERATION; PROGRESSION; EXPRESSION; PHENOTYPE; INVASION; MIRNAS;

D O I：

10.1166/jbn.2021.3066

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Tumour-associated macrophages (TAMs) are thought to contribute to oral squamous cell carcinoma (OSCC) initiation and progression. However, the underlying mechanism through which TAMs foster OSCC progression is still unclear. This study intended to determine whether there are exclusively exosomal miRNAs-derived macrophages that are functionally necessary for OSCC progression. The phenotype of TAM recruitment in OSCC tissue samples was assessed, subsequently identifying the influence of M2 macrophages and exosomes derived from M2 macrophages on OSCC proliferation and tumorigenesis in vitro and in vivo. CD68 and CD163, the specific markers of M2 type macrophages, were upregulated in TAMs presented in intra-cancer tissues. M2 macrophages and M2 macrophage-derived exosomes (M2 exos) both can promote OSCC growth and tumorigenicity. An exosomal RNA-seq analysis was conducted to predict regulatory exosomal miRNAs related to OSCC growth, which determined miR-31-5p and LATS2 for subsequent experiments. Mechanistically, miR-31-5p was delivered to recipient OSCC cells through M2 exos and complementary pairing with the large tumor suppressor 2 (LATS2) coding sequence, thus suppressing the expression of LATS2 and inactivation the Hippo signaling pathway to support OSCC growth. Collectively, our findings demonstrate that M2 macrophage-derived exosomal miR31-5p can make tumor suppressor LATS2 gene inhibited and facilitate the progression of OSCC via inhibiting the Hippo signaling pathway, which possibly provides new targets for the molecular therapy of OSCC.

引用

页码：822 / 837

页数：16