a Department of Otolaryngology Head and Neck Surgery , the First Affiliated Hospital of Zhengzhou University , Zhengzhou City , Henan Province , P. R. China.
Cancer Biol Ther. 2019;20(6):826-836. doi: 10.1080/15384047.2018.1564569. Epub 2019 Mar 25.
Laryngeal squamous cell carcinoma (LSCC) accounts for 95% of laryngeal cancer incidence. Tobacco use has been shown to have a linear association with the development of the disease. While early diagnosis and treatment of LSCC are critical in improving the 5-year survival rate and quality of life, diagnosis of early-stage LSCC remains challenging because of the unapparent symptoms. Here, we report that miR-506, a critical regulator in many types of cancers, is aberrantly suppressed in LSCC patient tissues and cultured cancer cells. This is likely responsible for the enhanced production of YAP1 protein, a transcriptional factor that is well known for its oncogenic roles in LSCC malignancy. Statistical analysis has confirmed that the expression levels of miR-506 and YAP1 are strongly correlated with the malignant statuses of patient tumors. Restoring the expression level of miR-506 in cultured LSCC cells significantly inhibited proliferation, migration and invasion of the cells. The miR-506 and YAP1 regulatory network seems to affect at least pathways involved in apoptosis. Our study, for the first time, has demonstrated a tumor suppressive role of miR-506 in LSCC. This opens new opportunities for further exploring the molecular details of the development of the disease and thus will facilitate the development of novel diagnosis and therapeutic strategies.
喉鳞状细胞癌(LSCC)占喉癌发病率的 95%。吸烟已被证明与疾病的发生呈线性相关。虽然早期诊断和治疗 LSCC 对于提高 5 年生存率和生活质量至关重要,但由于早期 LSCC 症状不明显,诊断仍然具有挑战性。在这里,我们报告 miR-506 是多种癌症的关键调节因子,在 LSCC 患者组织和培养的癌细胞中异常抑制。这可能导致 YAP1 蛋白的产生增强,YAP1 是一种转录因子,其在 LSCC 恶性肿瘤中的致癌作用是众所周知的。统计分析证实 miR-506 和 YAP1 的表达水平与患者肿瘤的恶性状态密切相关。在培养的 LSCC 细胞中恢复 miR-506 的表达水平显著抑制了细胞的增殖、迁移和侵袭。miR-506 和 YAP1 调控网络似乎至少影响了涉及细胞凋亡的途径。我们的研究首次证明了 miR-506 在 LSCC 中的肿瘤抑制作用。这为进一步探索疾病发展的分子细节提供了新的机会,从而将有助于开发新的诊断和治疗策略。