MiR-210 in exosomes derived from CAFs promotes non-small cell lung cancer migration and invasion through PTEN/PI3K/AKT pathway

被引：85

作者：

Yang, Fang ^{[1
]}

Yan, Yubo ^{[2
]}

Yang, Yang ^{[1
]}

Hong, Xuan ^{[1
]}

Wang, Meng ^{[1
]}

Yang, Zhaoyang ^{[1
]}

Liu, Baogang ^{[1
]}

Ye, Leiguang ^{[1
]}

机构：

[1] Harbin Med Univ, Canc Hosp, Dept Resp Med Oncol 1, 150 Haping Rd, Harbin 150081, Heilongjiang, Peoples R China

[2] Harbin Med Univ, Canc Hosp, Dept Thorac Surg, Harbin 150081, Heilongjiang, Peoples R China

来源：

CELLULAR SIGNALLING | 2020年 / 73卷

关键词：

Non-small cell lung cancer; CAFs; Exosome; MiR-210; UPF1; PTEN/PI3K/AKT; Epithelial-mesenchymal transition; SIGNALING PATHWAY; RNA DECAY; PROLIFERATION; PROGRESSION; METASTASIS; APOPTOSIS; UPF1;

D O I：

10.1016/j.cellsig.2020.109675

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Objective: Cancer-associated fibroblasts (CAFs) function as a crucial factor in tumor progression by carrying exosomes to neighboring cells. This study was assigned to expound the underlying mechanism of CAFs-derived exosomal miR-210 in non-small cell lung cancer (NSCLC) progression. Method: CAFs and normal fibroblasts (NFs) were isolated and identified. Exosomes secreted from CAFs and NFs were isolated to analyze their effects on tumor volume and epithelial-mesenchymal transition (EMT). Exosomal miR-210 expression level was measured. The effects of exosomal miR-210 and UPF1 on cell viability, EMT, PTEN/PI3K/AKT signal pathway were determined. Dual-luciferase reporter gene assay was utilized to validate the binding of UPF1 to miR-210. Results: CAFs-derived exosomes (CAFs-exo) were successfully extracted and proven to be uptake by lung cancer cells. Up-regulated expression level of miR-210 was found in CAFs-exo, which was then proved to enhance cell migration, proliferation, invasion abilities and EMT in NSCLC cells. Overexpression of miR-210 can also inhibit UPF1 and PTEN, but activate the PTEN/PI3K/AKT pathway. UPF1 was a target gene of miR-210. MiR-210 can up-regulate UPF1 expression level to activate PTEN/PI3K/AKT pathway. Conclusion: MiR-210 secreted by CAFs-exo could promote EMT by targeting UPF1 and activating PTEN/PI3K/AKT pathway, thereby promoting NSCLC migration and invasion.

引用

页数：12

共 43 条

[1] microRNA-210 overexpression inhibits tumor growth and potentially reverses gemcitabine resistance in pancreatic cancer [J].

Amponsah, Prince Saforo ;

Fan, Pei ;

Bauer, Nathalie ;

Zhao, Zhefu ;

Gladkich, Jury ;

Fellenberg, Joerg ;

Herr, Ingrid .

CANCER LETTERS, 2017, 388 :107-117

[2] Exosome-mediated delivery of miR-9 induces cancer-associated fibroblast-like properties in human breast fibroblasts [J].

Baroni, S. ;

Romero-Cordoba, S. ;

Plantamura, I. ;

Dugo, M. ;

D'Ippolito, E. ;

Cataldo, A. ;

Cosentino, G. ;

Angeloni, V. ;

Rossini, A. ;

Daidone, M. G. ;

Iorio, M. V. .

CELL DEATH & DISEASE, 2016, 7 :e2312-e2312

[3] Human nonsense-mediated RNA decay regulates EMT by targeting the TGF-ss signaling pathway in lung adenocarcinoma [J].

Cao, Lu ;

Qi, Lisha ;

Zhang, Lin ;

Song, Wangzhao ;

Yu, Yue ;

Xu, Cong ;

Li, Lingmei ;

Guo, Yuhong ;

Yang, Lingyi ;

Liu, Changxu ;

Huang, Qiujuan ;

Wang, Yalei ;

Sun, Baocun ;

Meng, Bin ;

Zhang, Bin ;

Cao, Wenfeng .

CANCER LETTERS, 2017, 403 :246-259

[4] Non-small-cell lung cancers: a heterogeneous set of diseases [J].

Chen, Zhao ;

Fillmore, Christine M. ;

Hammerman, Peter S. ;

Kim, Carla F. ;

Wong, Kwok-Kin .

NATURE REVIEWS CANCER, 2014, 14 (08) :535-546

[5] Downregulation of exosomal CLEC3B in hepatocellular carcinoma promotes metastasis and angiogenesis via AMPK and VEGF signals [J].

Dai, Wenjuan ;

Wang, Yilin ;

Yang, Tianxiao ;

Wang, Jing ;

Wu, Weicheng ;

Gu, Jianxin .

CELL COMMUNICATION AND SIGNALING, 2019, 17 (01)

[6] The emerging roles of exosomes in tumor-stroma interaction [J].

Fu, Hailong ;

Yang, Huan ;

Zhang, Xu ;

Xu, Wenrong .

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2016, 142 (09) :1897-1907

[7] Cancer-associated fibroblasts induce epithelial-mesenchymal transition of bladder cancer cells through paracrine IL-6 signalling [J].

Goulet, Cassandra Ringuette ;

Champagne, Audrey ;

Bernard, Genevieve ;

Vandal, Dominique ;

Chabaud, Stephane ;

Pouliot, Frederic ;

Bolduc, Stephane .

BMC CANCER, 2019, 19 (1)

[8] Exosomal miR-126 as a circulating biomarker in non-small-cell lung cancer regulating cancer progression [J].

Grimolizzi, Franco ;

Monaco, Federica ;

Leoni, Francesca ;

Bracci, Massimo ;

Staffolani, Sara ;

Bersaglieri, Cristiana ;

Gaetani, Simona ;

Valentino, Matteo ;

Amati, Monica ;

Rubini, Corrado ;

Saccucci, Franca ;

Neuzil, Jiri ;

Tomasetti, Marco ;

Santarelli, Lory .

SCIENTIFIC REPORTS, 2017, 7

[9] LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2 [J].

Han, Shuhua ;

Cao, Dandan ;

Sha, Jun ;

Zhu, Xiaoli ;

Chen, Dongqin .

MOLECULAR ONCOLOGY, 2020, 14 (05) :1074-1088

[10] Nuclear UPF1 Is Associated with Chromatin for Transcription-Coupled RNA Surveillance [J].

Hong, Dawon ;

Park, Taeyoung ;

Jeong, Sunjoo .

MOLECULES AND CELLS, 2019, 42 (07) :523-529

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