临沂人民医院:细胞外囊泡转移的miR-25促进大肠癌的发展和转移
  • 细胞外囊泡(EVs)可转移一系列生物活性信号、表面受体、编码蛋白的mRNA以及miRNA等;
  • SIRT6在代谢、炎症和衰老的调节中有重要作用;
  • 结直肠癌(CRC)细胞来源的EVs富集miR-25,并通过传递miR-25促进CRC细胞的活性和转移;
  • SIRT6通过下调Lin28b抑制NRP-1,从而抑制CRC细胞的活性和转移,而miR-25通过靶向并抑制SIRT6表达促进CRC细胞的恶性特征;
  • 荷瘤裸鼠实验证实,CRC细胞来源的EVs通过转移miR-25,抑制SIRT6,促进肿瘤的建立和转移。
主编推荐语
爱的抉择
癌症细胞来源的细胞外囊泡(EVs)可促进结直肠癌的进展,但调节机制不明。临沂人民医院的Qianfu Gao团队在Molecular Therapy - Nucleic Acids上发表文章,发现结直肠癌(CRC)细胞来源的EVs中富集miR-25,并将其转移至其他CRC细胞中,通过靶向并抑制SIRT6,从而促进CRC的进展和转移。
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Transfer of microRNA-25 by colorectal cancer cell-derived extracellular vesicles facilitates colorectal cancer development and metastasis

结直肠癌细胞来源的细胞外囊泡转移microRNA-25促进结直肠癌发展和转移

10.1016/j.omtn.2020.11.018

2020-11-25, Article

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Abstract:收起
Cancer cell-derived extracellular vesicles (EVs) have been reported to promote the progression of colorectal cancer (CRC), although the regulatory mechanism remains uncharacterized. In this study, we investigated the role of microRNA-25 (miR-25)/sirtuin 6 (SIRT6) in the contribution of EVs derived from CRC cells to progression of CRC. In a co-culture system with EVs from HCT116 and NCM460 cells, the viability, migratory, and invasive properties of SW480 and SW620 cells were evaluated by cell counting kit-8 (CCK-8) and Transwell assays. Luciferase, chromatin immunoprecipitation (ChIP), and RNA immunoprecipitation (RIP) assays were conducted to verify the interaction among miR-25, SIRT6, lin-28 homologB (Lin28b), and neuropilin-1 (NRP-1). It was established that HCT116 cell-derived EVs promoted the malignant properties of SW480 cells and SW620 cells by delivering miR-25. SIRT6 was targeted by miR-25, whereas SIRT6 inhibited NRP-1 through downregulation of Lin28b. The tumor-bearing nude mouse experiments substantiated that HCT116 cell-derived EVs transferred miR-25 to facilitate tumor formation and metastasis by inhibiting SIRT6. In summary, our study clarifies the involvement of miR-25-targeted SIRT6 inhibition and SIRT6-mediated inhibition of the Lin28b/NRP-1 axis in CRC cell-derived EVs to CRC progression and metastasis.

First Authors:
Shanchao Wang

Correspondence Authors:
Qianfu Gao

All Authors:
Shanchao Wang,Zeyan Zhang,Qianfu Gao

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