Department of Advanced Education in Orthodontic Dentistry, School of Dental Medicine, University of Nevada-Las Vegas, 1700 W. Charleston Boulevard, Las Vegas, NV 89106, USA.
Department of Clinical Sciences, School of Dental Medicine, University of Nevada-Las Vegas, 1700 W. Charleston Boulevard, Las Vegas, NV 89106, USA.
Int J Mol Sci. 2024 Feb 10;25(4):2167. doi: 10.3390/ijms25042167.
New evidence has suggested that non-coding microRNAs play a significant role in mediating and modulating chemotherapy resistance, particularly among oral cancers. One recent study found that the upregulation of miR-145 and the downregulation of miR-155 strongly correlated with a limited chemotherapy resistance to Cisplatin, 5-Fluorouracil, and Paclitaxel, although the mechanism(s) responsible for these observations remain unidentified. Using commercially available cell lines of oral squamous cell carcinoma, RNA was isolated, converted into cDNA, and subsequently screened for the expression of downstream targets of miR-145 and miR-155 using qPCR. These results demonstrated the upregulation of miR-21, miR-125, miR-133, miR-365, miR-720, and miR-1246, as well as the downregulation of miR-140, miR-152, miR-218, miR-221, and miR-224. This screening also confirmed the differential expression and regulation of mir-145 and miR-155 among the cell lines with limited chemotherapy resistance (SCC15). In addition, several downstream targets of specific microRNAs were upregulated by all oral cancer cell lines, such as and , or downregulated in all cell lines, such as , , , , SRGAP1, and . However, three miR-145 downstream targets were identified in the least chemotherapy-resistant cells, exhibiting the differential upregulation of and , as well as the downregulation of , with this expression pattern not detected in any of the other oral cancer cell lines. These data strongly support that the differential regulation of these three downstream targets may be related to the chemosensitivity of this oral cancer cell line. The potential involvement of these targets must be further investigated to determine how and whether mechanisms of these cellular pathways may be involved in the observed lack of chemotherapy resistance. These data may be important to design targets or treatments to reduce chemotherapy resistance and improve patient treatment outcomes.
新证据表明，非编码 microRNAs 在介导和调节化疗耐药性方面发挥着重要作用，尤其是在口腔癌中。最近的一项研究发现，miR-145 的上调和 miR-155 的下调与顺铂、5-氟尿嘧啶和紫杉醇的化疗耐药性有限密切相关，尽管这些观察结果的机制尚不清楚。使用市售的口腔鳞状细胞癌细胞系，分离 RNA，转化为 cDNA，然后使用 qPCR 筛选 miR-145 和 miR-155 的下游靶基因的表达。这些结果表明 miR-21、miR-125、miR-133、miR-365、miR-720 和 miR-1246 的上调，以及 miR-140、miR-152、miR-218、miR-221 和 miR-224 的下调。这种筛选还证实了具有有限化疗耐药性的细胞系（SCC15）中 mir-145 和 mir-155 的差异表达和调节。此外，几种特定 microRNAs 的下游靶基因在所有口腔癌细胞系中均上调，如和，或在所有细胞系中下调，如、、、、SRGAP1 和。然而，在最具化疗耐药性的细胞中鉴定出三个 miR-145 下游靶基因，表现出和的差异上调，以及的下调，这种表达模式在任何其他口腔癌细胞系中均未检测到。这些数据强烈支持这些三个下游靶基因的差异调节可能与该口腔癌细胞系的化疗敏感性有关。这些靶基因的潜在参与必须进一步研究，以确定这些细胞通路的机制如何以及是否可能参与观察到的化疗耐药性缺失。这些数据对于设计减少化疗耐药性和改善患者治疗效果的目标或治疗方法可能很重要。
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