Bifidobacterium longum Suppresses Murine Colorectal Cancer through the Modulation of oncomiRs and Tumor Suppressor miRNAs
Bifidobacterium longum Suppresses Murine Colorectal Cancer through the Modulation of oncomiRs and Tumor Suppressor miRNAs
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DOI：
10.1080/01635581.2019.1577984
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发表时间：
2019-05-19
影响因子：
2.9
通讯作者：
Shaaban, Mohamed T.
中科院分区：
文献类型：
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作者：
Fahmy, Cinderella A.;Gamal-Eldeen, Amira M.;Shaaban, Mohamed T.
使用在炎性溃疡性结肠炎模型上诱导的小鼠结直肠癌（CRC）研究了从女性母乳中分离的长双歧杆菌（BL）对一些致癌和肿瘤抑制miRNA以及IL-1 β和IL 6靶向miRNA的调节作用。对调节IL-6和IL-1 β表达的oncomiRs miR-21 a和miR-155的研究表明，在健康小鼠和CRC小鼠中，BL给药均抑制了这两种表达。BL-给药诱导肿瘤抑制miRNA（miR-145和miR-15 a）在健康小鼠和CRC-小鼠中的表达。在健康小鼠和CRC小鼠中，BL给药后，调节IL-1 β和IL-6表达的miR-146 a表达均降低。在CRC-小鼠中，NF-Kb浓度升高，然而在用BL处理后，这种NF-Kb诱导减少。BL显著提高健康小鼠IL-1 β和IL-6 mRNA和蛋白浓度。给CRC小鼠施用BL导致IL-1 β mRNA和IL-1 β浓度的显著增加，相反，这伴随着IL-6 mRNA和IL-6浓度的降低。BL给药导致CRC小鼠中异常隐窝病灶数量下降，结肠细胞坏死和纤维化增加。B的调节作用。longum对microRNA的作用可能通过抑制肿瘤细胞的增殖、侵袭、凋亡和细胞周期而在CRC中提供重要的治疗影响。
The modulatory role of the Bifidobacterium longum (BL), isolated from women breast milk, on some oncogenic and tumor suppressor miRNAs as well as IL-1 beta and IL6 targeted-miRNAs was investigated using murine colorectal cancer (CRC) induced on the top of inflammatory ulcerative colitis model. The investigation of the oncomiRs miR-21a and miR-155, which regulate IL-6 and IL-1 beta expression, indicated that both was depressed by BL-administration in healthy and in CRC-mice. BL-administration induced the tumor suppressor miRNAs (miR-145 and miR-15a) expression in both of the healthy and in CRC-mice. The miR-146a expression, which regulates both of IL-1 beta and IL-6 expression, was decreased after the BL-administration in both of the healthy and in CRC-mice. In CRC-mice, NF-Kb concentration was elevated, however this NF-Kb induction was diminished after the treatment with BL. BL highly enhanced the IL-1 beta and IL-6 mRNA and protein concentrations in healthy mice. The administration of BL to CRC-mice resulted in a dramatic increase in IL-1 beta mRNA and IL-1 beta concentration, which in contrast was accompanied with a decrease in the IL-6 mRNA and IL-6 concentration. BL-administration resulted in a drop in the aberrant crypt foci number in CRC-mice and increased necrosis and fibrosis of the colon cells. The modulatory influence of B. longum on microRNAs may provide an important therapeutic impact in CRC through inhibition of the proliferation, invasion, apoptosis, and cell cycle of tumor cells.