Hezova Renata, Kovarikova Alena, Srovnal Josef, Zemanova Milada, Harustiak Tomas, Ehrmann Jiri, Hajduch Marian, Sachlova Milana, Svoboda Marek, Slaby Ondrej
Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic.
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Tumour Biol. 2016 Jun;37(6):8007-18. doi: 10.1007/s13277-015-4656-8. Epub 2015 Dec 28.
Esophageal cancer is a malignant disease with poor prognosis, increasing incidence, and ineffective treatment options. MicroRNAs are post-transcriptional regulators of gene expression involved in many biological processes including carcinogenesis. We determined miR-205 expression levels in tumor/non-tumor tissues of 45 esophageal cancer patients using qPCR and found that decreased level of miR-205 in tumor tissue correlates with poor overall survival in esophageal adenocarcinoma patients. Further, we observed significantly higher levels of miR-205 in tumor tissue of esophageal squamous cell carcinoma. Ectopic overexpression of miR-205 in adenocarcinoma cell line SK-GT-4 led to decreased cell proliferation, cell cycle arrest in G1, and decreased migration ability. Conversely, in squamous cell line KYSE-150, same effects like inhibition of proliferation, migration, and colony-forming potential and cell cycle arrest in G2 were observed after silencing of miR-205. We performed global gene expression profiling and revealed that suppressive functioning of miR-205 in adenocarcinoma could be realized through regulation of epithelial-mesenchymal transition (EMT), whereas oncogenic in squamous cell carcinoma by regulation of metalloproteinase 10. Our results suggest that miR-205 could serve as biomarker in esophageal cancer and acts as a tumor suppressor in esophageal adenocarcinoma and oncogene in esophageal squamous cell carcinoma.
食管癌是一种预后较差、发病率不断上升且治疗选择无效的恶性疾病。微小RNA是参与包括致癌作用在内的许多生物学过程的基因表达的转录后调节因子。我们使用定量聚合酶链反应（qPCR）测定了45例食管癌患者肿瘤/非肿瘤组织中miR-205的表达水平，发现肿瘤组织中miR-205水平降低与食管腺癌患者的总体生存率较差相关。此外，我们观察到食管鳞状细胞癌肿瘤组织中miR-205水平显著更高。在腺癌细胞系SK-GT-4中异位过表达miR-205导致细胞增殖减少、细胞周期停滞在G1期以及迁移能力下降。相反，在鳞状细胞系KYSE-150中，沉默miR-205后观察到了类似的抑制增殖、迁移和集落形成潜能以及细胞周期停滞在G2期的效果。我们进行了全基因组表达谱分析，发现miR-205在腺癌中的抑制功能可通过调节上皮-间质转化（EMT）来实现，而在鳞状细胞癌中通过调节金属蛋白酶10发挥致癌作用。我们的结果表明，miR-205可作为食管癌的生物标志物，在食管腺癌中起肿瘤抑制作用，在食管鳞状细胞癌中起癌基因作用。
