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首页> 外文期刊>The FEBS journal >MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells
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MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells

机译:MicroRNA-143降低HCT116人结肠直肠癌细胞的生存力并提高对5-氟尿嘧啶的敏感性

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摘要

MicroRNAs are aberrantly expressed in cancer; microRNA-143 (miR-143) is down-regulated in colon cancer. HCT116 human colorectal cancer cells were used to investigate the biological role of miR-143. Transient miR-143 overexpression resulted in an approximate 60% reduction in cell viability. In addition, stable miR-143 overexpressing cells were selected with G418 and exposed to 5-fluorouracil. Increased stable expression of miR-143 was associated with decreased viability and increased cell death after exposure to 5-fluorouracil. These changes were associated with increased nuclear fragmentation and caspase -3, -8 and -9 activities. In addition, extracellular-regulated protein kinase 5, nuclear factor-B and Bcl-2 protein expression was down-regulated by miR-143, and further reduced by exposure to 5-fluorouracil. In conclusion, miR-143 modulates the expression of key proteins involved in the regulation of cell proliferation, death and chemotherapy response. In addition, miR-143 increases the sensitivity of colon cancer cells to 5-fluorouracil, probably acting through extracellular-regulated protein kinase 5uclear factor-B regulated pathways. Collectively, the data obtained in the present study suggest anti-proliferative, chemosensitizer and putative pro-apoptotic roles for miR-143 in colon cancer.
机译:MicroRNA在癌症中异常表达。 microRNA-143(miR-143)在结肠癌中被下调。 HCT116人类结直肠癌细胞用于研究miR-143的生物学作用。瞬时miR-143过表达导致细胞活力降低约60%。另外,用G418选择稳定的miR-143过表达细胞,并将其暴露于5-氟尿嘧啶。暴露于5-氟尿嘧啶后,miR-143稳定表达的增加与活力降低和细胞死亡增加相关。这些变化与增加的核碎片和caspase -3,-8和-9活性有关。此外,miR-143下调了细胞外调节的蛋白激酶5,核因子-B和Bcl-2蛋白的表达,并由于暴露于5-氟尿嘧啶而进一步降低。总之,miR-143调节参与调节细胞增殖,死亡和化学疗法应答的关键蛋白的表达。另外,miR-143可能会通过细胞外调节蛋白激酶5 /核因子B调节的途径发挥作用,从而增加结肠癌细胞对5-氟尿嘧啶的敏感性。总的来说,本研究中获得的数据表明miR-143在结肠癌中具有抗增殖,化学增敏作用和假定的促凋亡作用。

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