Department of Dermatology and Allergology, Ruhr-University Bochum, Bochum, Germany.
Cancer Invest. 2010 Jul;28(6):649-53. doi: 10.3109/07357901003630918.
Dysregulation of microRNA (miRNA) metabolism has been observed in a variety of human cancers. In this pilot study, we investigated expression profiles of the two most important enzymes of the miRNA machinery, Drosha and Dicer, in relation to epithelial skin cancer and its premalignant stage.
Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional) as well as from sites of healthy skin (intraindividual controls). Skin samples (n = 14) were also obtained from healthy subjects for additional controls. Dicer and Drosha mRNA levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction.
Drosha expression levels were significantly upregulated in both the BCC and SCC groups compared to those in the healthy controls (p < .01), while Dicer expression levels in the BCC group were significantly lower (p < .05). Dicer expression in the SCC group was significantly higher compared to intraindividual controls (p < .05), while Dicer expression levels in both the SCC and AK groups were not significantly different from healthy control samples (p > .05). In the premalignant AK group, we could not observe any significant difference in Drosha or Dicer expression levels compared to either healthy or intraindividual controls (p > .05).
We observed dysregulation of Drosha and Dicer expression in epithelial tumors when compared to healthy control samples. Therefore, we favor the hypothesis that miRNAs are involved in the carcinogenesis of epithelial skin cancer.
在各种人类癌症中观察到 microRNA(miRNA)代谢的失调。在这项初步研究中,我们研究了 miRNA 机制的两个最重要的酶 Drosha 和 Dicer 的表达谱与上皮性皮肤癌及其癌前阶段的关系。
本研究纳入了 6 例光化性角化病(AK)、15 例基底细胞癌(BCC)和 7 例鳞状细胞癌(SCC)患者。从肿瘤中心(病变部位)和健康皮肤部位(个体内对照)采集穿刺活检标本。还从健康受试者中获得了 14 份皮肤样本作为额外对照。通过实时定量逆转录聚合酶链反应检测 Dicer 和 Drosha 的 mRNA 水平。
与健康对照组相比,BCC 和 SCC 组的 Drosha 表达水平均显著上调(p <.01),而 BCC 组的 Dicer 表达水平显著降低(p <.05)。与个体内对照相比,SCC 组的 Dicer 表达显著升高(p <.05),而 SCC 和 AK 组的 Dicer 表达水平与健康对照样本无显著差异(p >.05)。在癌前 AK 组中,与健康或个体内对照相比,我们没有观察到 Drosha 或 Dicer 表达水平的任何显著差异(p >.05)。
与健康对照样本相比,我们观察到上皮性肿瘤中 Drosha 和 Dicer 的表达失调。因此,我们支持 miRNA 参与上皮性皮肤癌发生的假说。