Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer

被引:37
|
作者
Zhang, Yan [1 ]
Chen, Lin [2 ]
Ye, Xuanting [3 ]
Wu, Zhixiong [1 ]
Zhang, Zeyu [1 ]
Sun, Biaofeng [1 ]
Fu, Hong [1 ]
Fu, Chuangang [2 ]
Liang, Xiaofei [4 ]
Jiang, Hong [1 ]
机构
[1] Tongji Univ, Tongji Hosp, Sch Med, Dept Oncol, 389 Putuoxincun Rd, Shanghai 200065, Peoples R China
[2] Tongji Univ, Shanghai East Hosp, Sch Med, Dept Colorectal Surg,Dept Gen Surg, 150 Jimo Rd, Shanghai 200120, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Shanghai, Peoples R China
[4] Huzhou Lieyuan Med Lab Co Ltd, 800 Rujiadian Rd, Huzhou 313000, Peoples R China
基金
中国国家自然科学基金;
关键词
Gastric cancer; Exosomes; FOXM1; Long non coding RNA; Biomarker; TRANSCRIPTION FACTOR; PROMOTES; RESISTANCE; GROWTH; BILAYERS; MARKER;
D O I
10.1186/s12951-021-00873-w
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Forkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. Exosome was suggested to mediate cell communication by delivering active molecules in cancers. However, the existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (GC) were not clear. This study aims to investigate the potential role of FOXM1 related long noncoding RNA (FRLnc1) in exosomes in GC. Results: The prepared CD63 immunomagnetic beads (CD63-IMB) had the characteristics of good dispersity and high magnetic response. The isolated exosomes were presented with elliptical membranous particles under a transmission electron microscope (TEM), with the particle size of 89.78 +/- 4.8 nm. Western blot (WB) results showed that the exosomes were rich in CD9 and CD81. The Dil-labeled exosomes were distributed around cytoplasm and nucleus of cells by imaging flow cytometry (IFC) analysis. The results of quantitative real-time PCR (qRT-PCR) revealed that the FRLnc1 expressions were up-regulated in GC cells, tumor tissues, and serum of GC patients. An obviously upregulated FRLnc1 expression was found in serum exosomes of GC patients. Up-regulation of FRLnc1 expression was closely correlated to lymph node metastasis (LNM) and TNM stage with the combination of relevant clinicopathological parameter analysis. The in vitro functional analyses demonstrated that FRLnc1 knockdown by RNA interference suppressed cell proliferation and migration in HGC-27 cells, whereas FRLnc1 overexpression promoted cell proliferation and migration in MKN45 cells. After exosome treatment, the FRLnc1 expression was significantly increased in MKN45 cells, and the MKN45 cells showed increased ability of proliferation and migration. Conclusion: GC cells-derived exosomes played roles in promoting the growth and metastasis of GC by transporting FRLnc1, suggesting that FRLnc1 in the exosomes may be a potential biomarker for the diagnosis and treatment of GC. The delivery of FRLnc1 by the exosomes may provide a new way for the treatment of GC.
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页数:17
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