| 李 娜,李 赟,万小亚.MicroRNA-34a调控KLF4转录因子[J].中国肿瘤,2020,29(2):148-153. |
| MicroRNA-34a调控KLF4转录因子 |
| KLF4 Transcription Factor Regulated by MicroRNA-34a in 5-Fu Chemotherapy Resistance of Colorectal Cancer |
| 中文关键词 修订日期：2019-08-10 |
| DOI：10.11735/j.issn.1004-0242.2020.02.A011 |
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| 中文关键词: 结直肠癌 5-氟尿嘧啶 耐药 miR-34a KLF4 |
| 英文关键词:colorectal cancer 5-fluorouracil drug resistance miR-34a Krüppel-like factor 4（KLF4） |
| 基金项目:国家自然科学基金（81660400） |
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| 摘要点击次数: 1393 |
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| 中文摘要: |
| 摘 要：［目的］ 研究microRNA-34a（miR-34a）与其靶基因KLF4转录因子在结直肠癌发生化疗耐药中的作用。［方法］ 利用miRDB和microRNA公共数据库筛选出miR-34a的直接作用靶点KLF4 3′-UTR区。运用real-time PCR方法检测人5-氟尿嘧啶（5-Fu）耐药和敏感的结直肠癌组织及癌旁组织中miR-34a与KLF4的表达水平；建立5-Fu抵抗性结直肠癌细胞系，运用real-time PCR方法检测耐药细胞中KLF4的表达；上调5-Fu耐药结直肠癌细胞中miR-34a的表达，明确在结直肠癌5-Fu耐药细胞系中miR-34a对KLF4的调控作用。［结果］ 在40例5-Fu耐药的结直肠癌组织中miR-34a呈低表达，KLF4呈高表达，且miR-34a在癌组织及癌旁组织中的表达与KLF4呈显著负相关（r=-0.678，P<0.001）；在5-Fu耐药结直肠癌细胞系HCT-8/5-Fu和SW-480/5-Fu中KLF4呈高表达，且上调耐药细胞中miR-34a可抑制耐药细胞中KLF4的表达。［结论］ KLF4转录因子在5-Fu化疗耐药的结直肠癌组织中呈低表达，并与miR-34a呈负相关，上调miR-34a的表达可直接抑制KLF4的表达，提示miR-34a负向调控KLF4具有逆转结直肠癌细胞化疗耐药的可能。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the role of microRNA-34a（miR-34a） and its target gene Krüppel-like factor 4（KLF4） transcription factor in chemotherapy resistance of colorectal cancer.［Methods］ KLF4 3′-UTR region was screened as the direct target region of miR-34a by using miRDB and microRNA public databases. The expression level of miR-34a and KLF4 in human 5-Fu resistant and sensitive colorectal cancer tissues and adjacent tissues was detected by the real-time PCR. 5-Fu resistant colorectal cancer cell line was established and the expression of KLF4 in drug resistant colorectal cancer cells was detected by real-time PCR.The expression of miR-34a in 5-Fu resistant colorectal cancer cells was up-regulated，and the regulatory effect of miR-34a on KLF4 in 5-Fu resistance colorectal cancer cells was confirmed.［Results］ In 40 cases of 5-Fu resistant colorectal cancer，the expression of miR-34a was low and the expression of KLF4 was high，and the expression of miR-34a in cancer tissues and adjacent tissues was negatively correlated with KLF4（r=-0.678，P<0.001）. The high expression of KLF4 was detected in 5-Fu resistant colorectal cancer HCT-8/5-Fu cells and SW-480/5-Fu cells；and the up-regulation of miR-34a inhibited the expression of KLF4 in drug-resistant colorectal cells.［Conclusion］ The expressionof KLF4 transcription factor is low in 5-Fu resistant colorectal cancer and it is negatively correlated with miR-34a. Up-regulating the expression of miR-34a can inhibit the expression of KLF4，suggesting that the negative regulation of KLF4 by miR-34a may reverse the chemotherapy resistance of colorectal cancer cells. |
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