Liang Yancan, Ye Jiantao, Jiao Jiuyang, Zhang Jin, Lu Yingjuan, Zhang Li, Wan Di, Duan Liming, Wu You, Zhang Bin
Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityGuangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangzhou Higher Education Institutes, Sun Yat-Sen UniversityGuangzhou, China.
Department of Internal Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, China.
Am J Transl Res. 2017 Mar 15;9(3):1101-1113. eCollection 2017.
Salivary adenoid cystic carcinoma (SACC) is a relatively uncommon epithelial-like malignancy that can occur in the head and neck region. Despite its slow growth, this aggressive salivary gland tumor frequently recurs and metastasizes to distant organs since lacking effective chemotherapy treatment. MicroRNAs are key regulators in tumor metastasis and progression, but their roles during SACC progression have not been illustrated. In current study, we demonstrate that miR-125a-5p is down-regulated in SACC and closely related to the metastasis and progression in human SACC specimens. In vitro, miR-125a-5p mimic can suppress SACC cell migration and invasion; while blocking miR-125a-5p can relieve the inhibition effect. By using dual-luciferase assay, we confirmed that miR-125a-5p directly targeted to p38 and tissue samples of patients indicated the negative correlation between miR-125a-5p and p38; clinical analysis also showed that low level expression of miR-125a-5p is closely associated with poor prognosis of SACC. Furthermore, down-regulation of miR-125a-5p triggered downstream p38/JNK/ERK activation. Taken together, our results indicate that down-regulation of miR-125a-5p promotes SACC progression through p38 signal pathway and miR-125a-5p can be a potential therapeutic target of SACC.
涎腺腺样囊性癌（SACC）是一种相对罕见的上皮样恶性肿瘤，可发生于头颈部区域。尽管其生长缓慢，但这种侵袭性唾液腺肿瘤由于缺乏有效的化疗治疗，经常复发并转移至远处器官。微小RNA是肿瘤转移和进展的关键调节因子，但其在SACC进展过程中的作用尚未阐明。在本研究中，我们证明miR-125a-5p在SACC中表达下调，且与人类SACC标本的转移和进展密切相关。在体外，miR-125a-5p模拟物可抑制SACC细胞迁移和侵袭；而阻断miR-125a-5p可解除这种抑制作用。通过双荧光素酶测定，我们证实miR-125a-5p直接靶向p38，患者的组织样本显示miR-125a-5p与p38呈负相关；临床分析还表明，miR-125a-5p低水平表达与SACC的不良预后密切相关。此外，miR-125a-5p的下调触发了下游p38/JNK/ERK的激活。综上所述，我们的结果表明，miR-125a-5p的下调通过p38信号通路促进SACC进展，miR-125a-5p可能是SACC的潜在治疗靶点。
