Cai Yi, Liu Jie, Cai Shao-Kang, Miao Er-Ya, Jia Cheng-Qian, Fan Yong-Zhi, Li Ying-Bo
Department of Pain Management, The Center Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Department of Pathology, The Center Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Onco Targets Ther. 2020 Jun 15;13:5605-5616. doi: 10.2147/OTT.S237562. eCollection 2020.
It is well known that diet Eicosapentaenoic acid (EPA) is beneficial to colon cancer (CC). However, the underlying molecular mechanisms of EPA-relating miRNAs on genesis and development of this area is still unclear.
This study tries to find the function and specific role of EPA in CC through quantitative PCR (qPCR), Western blotting, immunofluorescence (IF), mass spectrometry, and immunohistochemistry (IHC) assays. By these methods, the enrichment of 15-LOX-1 metabolites of EPA, the expression of miR-101 and Cox2, and the relationship among them in CC are measured.
The quantity of miR-101 was obviously suppressed in CC tissues and SW480 cells. After application of miR-101 mimics in CC cell lines, the Cox2 expression was inhibited too. Next, we confirmed that EPA could increase the expression of miR-101 induced by 15-LOX-1. Finally, we tested whether EPA functions as a regulator of miR-101 via the production of resolvin E3.
Our data demonstrate that the EPA-15-LOX-1-miR-101-Cox2 signaling pathway owns a crucial position in the pathogenesis and development of diet-related CC. These findings exert exciting meanings for presenting new therapeutic angles in CC.
众所周知，膳食中的二十碳五烯酸（EPA）对结肠癌（CC）有益。然而，与EPA相关的微小RNA（miRNA）在该领域发生和发展中的潜在分子机制仍不清楚。
本研究试图通过定量聚合酶链反应（qPCR）、蛋白质免疫印迹法、免疫荧光（IF）、质谱分析和免疫组织化学（IHC）检测来发现EPA在结肠癌中的功能和具体作用。通过这些方法，检测了EPA的15-脂氧合酶-1（15-LOX-1）代谢产物的富集情况、miR-101和环氧化酶2（Cox2）的表达以及它们在结肠癌中的相互关系。
miR-101的量在结肠癌组织和SW480细胞中明显受到抑制。在结肠癌细胞系中应用miR-101模拟物后，Cox2的表达也受到抑制。接下来，我们证实EPA可以增加由15-LOX-1诱导的miR-101的表达。最后，我们测试了EPA是否通过生成消退素E3作为miR-101的调节因子。
我们的数据表明，EPA-15-LOX-1-miR-101-Cox2信号通路在饮食相关结肠癌的发病机制和发展中具有关键地位。这些发现为在结肠癌中呈现新的治疗角度具有令人兴奋的意义。
