Eicosapentaenoic acid’s metabolism of 15-LOX-1 promotes the expression of miR-101 thus inhibits Cox2 pathway in colon cancer

Yi Cai,1,* Jie Liu,2,* Shao-kang Cai,1 Er-ya Miao,1 Cheng-qian Jia,1 Yong-zhi Fan,1 Ying-bo Li1 1Department 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; 2Department of Pathology, The Center Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying-bo Li; Yong-zhi FanDepartment of Pain Management, The Center Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, 26 Shengli Street, Jiang’an, Wuhan, Hubei 430014, People’s Republic of ChinaEmail eyyttk@126.com; ryan7688@qq.comPurpose: 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.Materials and Methods: 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.Results: 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.Conclusion: 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.Keywords: colon cancer, 15-LOX-1, miR-101, Cox2, EPA