Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Br J Cancer. 2013 May 14;108(9):1817-21. doi: 10.1038/bjc.2013.175. Epub 2013 Apr 16.
MicroRNAs (miRNAs) are involved in essential biological activities, and have been reported to exhibit differential expression profiles in various cancers. Our previous study demonstrated that intercellular adhesion molecule-2 (ICAM2) inhibition induces radiosensitisation in oral squamous cell carcinoma (OSCC) cells. Thus, we hypothesised that certain miRNAs play crucial roles in radioresistance in OSCC by regulating ICAM2 expression.
Because predicted target gene analyses revealed that microRNA-125b (miR-125b) potentially regulates ICAM2 mRNA expression, we examined the association between miR-125b and radioresistance. The expression of miR-125b was investigated by real-time quantitative reverse transcriptase-PCR. For a functional analysis, miR-125b was transfected to OSCC-derived cells.
A downregulated expression of miR-125b was found in OSCC-derived cell lines and OSCC samples. The miR-125b-transfected cells showed a decreased proliferation rate, enhanced radiosensitivity to X-ray irradiation and diminished ICAM2 mRNA expression. Moreover, miR-125b expression correlated with OSCC tumour staging and survival.
These findings suggested that the downregulated miR-125b expression was associated with proliferation and radioresistance mechanisms, probably through ICAM2 signalling. Thus, controlling the expression or activity of miR-125b might contribute to suppressing proliferation and overcoming radioresistance in OSCC.
微小 RNA(miRNAs)参与重要的生物活动,并且已经在各种癌症中表现出差异表达谱。我们之前的研究表明,细胞间黏附分子-2(ICAM2)的抑制可诱导口腔鳞状细胞癌(OSCC)细胞的放射增敏。因此,我们假设某些 miRNA 通过调节 ICAM2 表达在 OSCC 中对放射抵抗起关键作用。
由于预测的靶基因分析表明微小 RNA-125b(miR-125b)可能调节 ICAM2 mRNA 的表达,我们研究了 miR-125b 与放射抵抗之间的关系。通过实时定量逆转录 PCR 检测 miR-125b 的表达。为了进行功能分析,将 miR-125b 转染至 OSCC 衍生的细胞中。
在 OSCC 衍生的细胞系和 OSCC 样本中发现 miR-125b 的表达下调。miR-125b 转染的细胞表现出增殖率降低、对 X 射线照射的放射敏感性增强以及 ICAM2 mRNA 表达减少。此外,miR-125b 的表达与 OSCC 肿瘤分期和生存相关。
这些发现表明,下调的 miR-125b 表达与增殖和放射抵抗机制有关,可能通过 ICAM2 信号通路。因此,控制 miR-125b 的表达或活性可能有助于抑制 OSCC 细胞的增殖并克服放射抵抗。