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

PURPOSE: 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.

KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats.

Potassium-chloride cotransporter 2 (KCC2) has been indicated to serve a crucial role during chronic neuropathic pain (NP). Following the emergence of NP, γ­aminobutyric acid (GABA) A receptor­mediated signaling may be further impaired by the changes of KCC2 chloride anion gradient. In the present study, the authors investigate the effect of electro-acupuncture (EA) on the behavior and the expression of KCC2 and GABAA receptor γ2 subunit in the spinal cord of chronic constriction injury (CCI) model rats. A total of 60 adult male Sprague­Dawley rats were divided into four groups: Normal group, sham­CCI group, CCI group and CCI+EA group. The effect of EA was assessed via the values of mechanical withdrawal threshold and thermal withdrawal latency, which were significantly improved upon stimulation of the ST­36 and GB­34 acupoints. In addition, a marked reduction in both the mRNA and protein levels of KCC2 and GABAA receptor γ2 subunit was observed in the spinal cord following loose ligation of the sciatic nerve. The reductions in KCC2 and GABAA receptor γ2 subunit expression were reversed by EA treatment. These results support the notion that KCC2 and GABAA receptor γ2 subunit contribute to NP following peripheral nerve injury and extend the understanding of the analgesic effects of EA on NP.