河北医科大学学报 ›› 2023, Vol. 44 ›› Issue (10): 1133-1140.doi: 10.3969/j.issn.1007-3205.2023.10.004

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miRNA对口腔鳞状细胞癌化疗耐药性的调控机制研究

  

  1. 1.河北省石家庄市人民医院口腔科，河北 石家庄050000；2.河北医科大学第四医院口腔科，河北 石家庄 050017;3.河北大学附属医院口腔科,河北 保定 071000

  • 出版日期:2023-10-25 发布日期:2023-11-03
  • 作者简介:翟文静（1986-），女，河北辛集人，河北省石家庄市人民医院主治医师，医学硕士，从事口腔黏膜癌前病变诊治研究。
  • 基金资助:
    国家癌症中心攀登基金临床研究课题（NCC201803B006）；河北省医学科学研究重点课题项目（20200102）

Regulatory mechanism of miRNA on chemoresistance of oral squamous cell carcinoma

  1. 1.Department of Stomatology, the People′s Hospital of Shijiazhuang City, Hebei Province, Shijiazhuang 
    050000, China; 2.Department of Stomatology, the Fourth Hospital of Hebei Medical University, 
    Shijiazhuang 050017, China; 3.Department of  Stomatology, Affiliated Hospital of 
    Hebei University, Baoding 071000, China

  • Online:2023-10-25 Published:2023-11-03

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摘要： 目的 探讨特征性微核糖核酸(microRNA,miRNA)在口腔鳞状细胞癌（oral squamous cell carcinoma,OSCC）化疗耐药性和肿瘤生物学中的作用。
方法 在耐药OSCC中SCC084/R、SCC131/R和SCC9/R中选择3个表达异常的miRNA（miR-27b-5p、 miR-130a-3p和 miR-125a-5p）。评估所选miRNA对OSCC耐药细胞系的细胞毒性、细胞凋亡和细胞周期的影响。随后，通过miRNA靶基因预测数据库TargetScan选择miRNA的潜在靶点，通过Western blotting对相应靶点蛋白表达进行分析。
结果 miR-27b-5p和miR-130a-3p可提高SCC084/R、SCC131/R和SCC9/R细胞对顺铂的敏感性，而miR-125a-5p仅能提高SCC9/R对顺铂的敏感性(P＜0.05)。miR-27b-5p上调可提高SCC9/R细胞对5-氟尿嘧啶(5-fluorouracil,5-FU)的敏感性，miR-130a-3p下调可提高SCC084/R细胞对5-FU的敏感性（P＜0.05）。相对于单个miRNA转染，共转染miRNA在SCC084/R和SCC131/R耐药细胞系中显示出更强的化疗增敏作用（P＜0.05）。所选miRNA均能引起细胞凋亡，除miR-130a-3p外，miR-125a-5p和miR-27b-5p均能引起SCC084/R和SCC131/R细胞的G1期阻滞。耐药调控涉及ErbB2/Her2通路、p38通路、p53通路及通路的多个下游靶点。
结论 miRNA可能是调控OSCC耐药性的关键因素，且这种调控具有多靶点性。


关键词: 口腔肿瘤, 微RNAs, 药物疗法, 耐药

Abstract: Objective The role of characteristic microRNA (miRNA) in chemoresistance and tumor biology of oral squamous cell carcinoma(OSCC). 
Methods Three miRNAs with abnormal expression (miR-27b-5p, miR-130a-3p and miR-125a-5p) were selected from three drug-resistant OSCC cell lines SCC084/R,SCC131/R and SCC9/R. The effects of those miRNAs on cytotoxicity, apoptosis and cell cycle were evaluated in drug-resistant OSCC cell lines. Subsequently, the potential targets of miRNA were selected by Target gene prediction database TargetScan. The expression of those potential targets was evaluated by Western blotting. 
Results miR-27b-5p and miR-130a-3p could enhance the sensitivity of SCC084/R, SCC131/R and SCC9/R to cisplatin, while miR-125a-5p could only improve sensitivity of SCC9/R to cisplatin (P＜0.05). Upregulation of miR-27b-5p could increase the sensitivity of SCC9/R cells to 5-fluorouracil (5-FU), while down regulation of miR-130a-3p could increase the sensitivity of SCC084/R cells to 5-FU (P＜0.05). Compared with single miRNA transfection, co-transfected miRNA showed better chemo-sensitization in drug-resistant cell lines SCC084/Rand SCC131/R (P＜0.05). Selected miRNAs were able to cause cell apoptosis, except miR-130a-3p, and both miR-125a-5p and miR-27b-5p show preference to arrest SCC084/R and SCC131/R in G1 phase. The regulation of drug resistance involved ErbB2/Her2 pathway, p38 pathway, p53 pathway and its downstream targets. 
Conclusion miRNA may be a key factor in the regulation of drug resistance in OSCC, and multiple targets are involved during the process of regulation.


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