MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells
MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells
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DOI：
10.1111/j.1742-4658.2009.07383.x
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发表时间：
2009-11-01
期刊：
影响因子：
5.4
通讯作者：
Rodrigues, Cecilia M. P.
中科院分区：
文献类型：
--
作者：
Borralho, Pedro M.;Kren, Betsy T.;Rodrigues, Cecilia M. P.
microRNA在癌症中异常表达; microRNA-143（miR-143）在结肠癌中下调。使用HCT 116人结直肠癌细胞来研究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%。此外，用G418选择稳定的miR-143过表达细胞并暴露于5-氟尿嘧啶。miR-143的稳定表达增加与暴露于5-氟尿嘧啶后细胞活力降低和细胞死亡增加相关。这些变化与核碎片和caspase-3、-8和-9活性增加有关。此外，细胞外调节蛋白激酶5、核因子-κ B和Bcl-2蛋白表达被miR-143下调，并通过暴露于5-氟尿嘧啶进一步降低。总之，miR-143调节参与调节细胞增殖、死亡和化疗反应的关键蛋白的表达。此外，miR-143增加结肠癌细胞对5-氟尿嘧啶的敏感性，可能通过细胞外调节的蛋白激酶5/核因子-κ B调节途径起作用。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、化疗增敏和推定的促凋亡作用。
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-kappa 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 5/nuclear factor-kappa 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.