Guan Guofang, Zhang Dejun, Zheng Ying, Wen Lianji, Yu Duojiao, Lu Yanqing, Zhao Yan
Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University Changchun 130041, P. R. China.
Department of Otolaryngology, Head and Neck Surgery, Tumor Hospital of Jilin Province Changchun 130012, P. R. China.
Int J Clin Exp Pathol. 2014 Aug 15;7(9):5683-91. eCollection 2014.
Despite of the variety of combined modality treatments for laryngeal carcinoma have been introduced, the distance recurrence rate and 5-year overall survival rate over the past decades are still the major issues, underlining the importance to better understand the biological bases that contribute to disease progression. Here, we reported that miR-423-3p overexpressed in primary laryngeal carcinoma cell line where it plays a critical role in tumor progression. Suppression of miR-423-3p expression resulted in decreasing cell proliferation, clonogenicity, cell migration and invasion. By using in silico prediction algorithms for target identification, AdipoR2 (adiponectin receptor 2) and DUSP4 (MAP kinase phosphatase 2) were identified to be potential targets of miR-423-3p. Overexpression of miR-423-3p was associated with epigenetic silencing of AdipoR2 in human laryngeal carcinoma samples, which have been previously implicated in suppression of tumor proliferation and angiogenesis. Luciferase reporter assays and western blot further confirmed the direct interaction of miR-423-3p with AdipoR2. Our findings have demonstrated that miR-423-3p plays an important oncogenic role in laryngeal carcinoma progression, and further suggest that suppression of miR-423-3p expression might be useful for its clinical management.
尽管已经引入了多种喉癌联合治疗方式，但在过去几十年里，远处复发率和5年总生存率仍然是主要问题，这凸显了更好地理解导致疾病进展的生物学基础的重要性。在此，我们报告了miR-423-3p在原发性喉癌细胞系中过表达，并且在肿瘤进展中起关键作用。抑制miR-423-3p的表达导致细胞增殖、克隆形成能力、细胞迁移和侵袭能力下降。通过使用计算机预测算法进行靶点识别，确定脂联素受体2（AdipoR2）和双特异性磷酸酶4（DUSP4）是miR-423-3p的潜在靶点。在人喉癌样本中，miR-423-3p的过表达与AdipoR2的表观遗传沉默有关，AdipoR2此前被认为与抑制肿瘤增殖和血管生成有关。荧光素酶报告基因检测和蛋白质印迹进一步证实了miR-423-3p与AdipoR2之间的直接相互作用。我们的研究结果表明，miR-423-3p在喉癌进展中起重要的致癌作用，进一步表明抑制miR-423-3p的表达可能对其临床治疗有用。
