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MiR-346-5p promotes colorectal cancer cell proliferation in vitro and in vivo by targeting FBXL2 and activating the β-catenin signaling pathway.
Life Sciences ( IF 5.2 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.lfs.2020.117300 Shuang Pan 1 , Wei Wu 2 , Fu Ren 2 , Lei Li 3 , Yao Li 1 , Weihong Li 1 , Aimei Wang 1 , Dahua Liu 2 , Yongyan Dong 4
Life Sciences ( IF 5.2 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.lfs.2020.117300 Shuang Pan 1 , Wei Wu 2 , Fu Ren 2 , Lei Li 3 , Yao Li 1 , Weihong Li 1 , Aimei Wang 1 , Dahua Liu 2 , Yongyan Dong 4
Affiliation
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MiR-346-5p is overexpressed in several cancers, including colorectal cancer (CRC). However, the effects of miR-346-5p on CRC progression have not yet been clarified. In our study, miR-346-5p levels in four CRC cell lines and normal human colon epithelial cells were determined by real-time PCR. SW620 and HCT116 cells were selected and then transfected with miR-346-5p mimic, miR-346-5p inhibitor, or specific siRNAs targeting F-box/LRR-repeat protein 2 (FBXL2). Cell proliferation, cell cycle distribution and cell cycle regulators were examined by CCK-8 assay, flow cytometry, and western blot. The binding of miR-346-5p on 3' untranslated region (UTR) of FBXL2 were verified by dual-luciferase reporter assay. CRC cells were co-transfected with miR-346-5p inhibitor and siFBXL2 to investigate the involvement of FBXL2. Interaction of FBXL2 with forkhead box M1 (FoxM1) was examined by co-immunoprecipitation (Co-IP) assay. The effect of miR-346-5p knockdown on CRC tumorigenesis in vivo was investigated. Here, we found that miR-346-5p overexpression promoted, while miR-346-5p knockdown inhibited cell proliferation and G1-S transition. Inhibition of FBXL2 showed similar effects as miR-346-5p overexpression. Moreover, we verified that FBXL2 was a direct target of miR-346-5p. FBXL2 interacted with FoxM1, and then negatively regulated both FoxM1 and nuclear β-catenin levels. Additionally, FBXL2 knockdown reversed the effects of miR-346-5p inhibitor. In xenograft models, miR-346-5p knockdown significantly inhibited tumor growth, increased FBXL2 expression, and downregulated the levels of FoxM1 and nuclear β-catenin. In conclusion, miR-346-5p may promote CRC growth by targeting FBXL2 and activating the β-catenin signaling pathway. MiR-346-5p may be a novel target in cancer therapy.
中文翻译：
MiR-346-5p通过靶向FBXL2和激活β-catenin信号传导途径，在体外和体内促进大肠癌细胞的增殖。
MiR-346-5p在几种癌症（包括结直肠癌（CRC））中过表达。然而，miR-346-5p对CRC进展的影响尚未阐明。在我们的研究中，通过实时PCR测定了四种CRC细胞系和正常人结肠上皮细胞中的miR-346-5p水平。选择SW620和HCT116细胞，然后用miR-346-5p模拟物，miR-346-5p抑制剂或靶向F-box / LRR重复蛋白2（FBXL2）的特定siRNA转染。通过CCK-8测定，流式细胞术和蛋白质印迹检查细胞增殖，细胞周期分布和细胞周期调节剂。通过双荧光素酶报告基因分析证实了miR-346-5p在FBXL2的3'非翻译区（UTR）上的结合。将CRC细胞与miR-346-5p抑制剂和siFBXL2共转染，以研究FBXL2的参与。FBXL2与叉头盒M1（FoxM1）的相互作用通过免疫共沉淀（Co-IP）分析进行了检查。研究了miR-346-5p敲低对体内CRC肿瘤发生的影响。在这里，我们发现miR-346-5p的过表达促进了，而miR-346-5p的抑制了细胞增殖和G1-S过渡。FBXL2的抑制显示与miR-346-5p过表达相似的作用。此外，我们证实FBXL2是miR-346-5p的直接靶标。FBXL2与FoxM1相互作用，然后负调控FoxM1和核β-连环蛋白水平。此外，FBXL2组合式逆转了miR-346-5p抑制剂的作用。在异种移植模型中，miR-346-5p敲低可显着抑制肿瘤生长，增加FBXL2表达，并下调FoxM1和核β-连环蛋白的水平。结论，miR-346-5p可通过靶向FBXL2并激活β-catenin信号通路来促进CRC的生长。MiR-346-5p可能是癌症治疗中的新型靶标。
更新日期：2020-01-15
中文翻译：
MiR-346-5p通过靶向FBXL2和激活β-catenin信号传导途径，在体外和体内促进大肠癌细胞的增殖。
MiR-346-5p在几种癌症（包括结直肠癌（CRC））中过表达。然而，miR-346-5p对CRC进展的影响尚未阐明。在我们的研究中，通过实时PCR测定了四种CRC细胞系和正常人结肠上皮细胞中的miR-346-5p水平。选择SW620和HCT116细胞，然后用miR-346-5p模拟物，miR-346-5p抑制剂或靶向F-box / LRR重复蛋白2（FBXL2）的特定siRNA转染。通过CCK-8测定，流式细胞术和蛋白质印迹检查细胞增殖，细胞周期分布和细胞周期调节剂。通过双荧光素酶报告基因分析证实了miR-346-5p在FBXL2的3'非翻译区（UTR）上的结合。将CRC细胞与miR-346-5p抑制剂和siFBXL2共转染，以研究FBXL2的参与。FBXL2与叉头盒M1（FoxM1）的相互作用通过免疫共沉淀（Co-IP）分析进行了检查。研究了miR-346-5p敲低对体内CRC肿瘤发生的影响。在这里，我们发现miR-346-5p的过表达促进了，而miR-346-5p的抑制了细胞增殖和G1-S过渡。FBXL2的抑制显示与miR-346-5p过表达相似的作用。此外，我们证实FBXL2是miR-346-5p的直接靶标。FBXL2与FoxM1相互作用，然后负调控FoxM1和核β-连环蛋白水平。此外，FBXL2组合式逆转了miR-346-5p抑制剂的作用。在异种移植模型中，miR-346-5p敲低可显着抑制肿瘤生长，增加FBXL2表达，并下调FoxM1和核β-连环蛋白的水平。结论，miR-346-5p可通过靶向FBXL2并激活β-catenin信号通路来促进CRC的生长。MiR-346-5p可能是癌症治疗中的新型靶标。
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