Li Yue-Ju, Lai Wei-Ting, Chang Cheng-Chi, Kuo Mark Yen-Ping, Deng Yi-Ting, Yang Cheng-Ning, Cheng Shih-Jung, Wu Tai-Sheng, Chen Szu-Ta, Lin Been-Ren
Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taiwan; Angiogenesis Research Center, National Taiwan University, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taiwan.
Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taiwan.
Oral Oncol. 2017 Mar;66:100-107. doi: 10.1016/j.oraloncology.2016.11.006. Epub 2016 Dec 21.
Relapse is the most serious problem affecting the morbidity and mortality rates of patients with head and neck squamous cell carcinoma (HNSCC). Although HNSCC has been studied for several decades, the exact mechanism of cancer recurrence remains unclear.
ataxia-telangiectasia mutated interactor (ATMIN) messenger RNA(mRNA) expression was detected in HNSCC samples by quantitative RT-PCR, and was analyzed with patients' clinical outcomes by Kaplan-Meier analyses. The ectopic ATMIN expression or ATMIN silencing on invasion ability was evaluated in HNSCC cell lines. Lymph node metastasis ability was investigated by buccal orthotopic implantation in vivo. All statistical tests were two-sided.
ATMIN mRNA expression was positively correlated with patients' clinical outcomes. ATMIN blockage reduced invasion, migration, and metastasis abilities both in vitro and in vivo. Evidence from a buccal orthotopic implantation mice model showed that silenced ATMIN expression prolongs mice survival and reduced lymph node metastasis. In high-throughput microarray and bioinformative analyses, KRas was identified as a crucial downstream effector in ATMIN-mediated HNSCC metastasis and was positively associated with patients' clinical stages and ATMIN mRNA expression.
The role of ATMIN and its regulatory mechanisms in HNSCC progression are reported for the first time. The study results improve our understanding of the ATMIN-KRas axis leading to HNSCC migration or invasion and metastasis and facilitates the identification of possible therapy targets of downstream genes for designing effective therapeutic strategies in personalized medicine.
复发是影响头颈部鳞状细胞癌（HNSCC）患者发病率和死亡率的最严重问题。尽管对HNSCC已经研究了几十年，但癌症复发的确切机制仍不清楚。
通过定量逆转录聚合酶链反应（RT-PCR）检测HNSCC样本中共济失调毛细血管扩张症突变相互作用蛋白（ATMIN）信使核糖核酸（mRNA）的表达，并通过Kaplan-Meier分析将其与患者的临床结果进行分析。在HNSCC细胞系中评估异位ATMIN表达或ATMIN沉默对侵袭能力的影响。通过体内颊部原位植入研究淋巴结转移能力。所有统计检验均为双侧检验。
ATMIN mRNA表达与患者的临床结果呈正相关。ATMIN阻断在体外和体内均降低了侵袭、迁移和转移能力。颊部原位植入小鼠模型的证据表明，沉默的ATMIN表达可延长小鼠存活时间并减少淋巴结转移。在高通量微阵列和生物信息学分析中，KRas被确定为ATMIN介导的HNSCC转移中的关键下游效应因子，并且与患者的临床分期和ATMIN mRNA表达呈正相关。
首次报道了ATMIN在HNSCC进展中的作用及其调控机制。研究结果增进了我们对导致HNSCC迁移、侵袭和转移的ATMIN-KRas轴的理解，并有助于识别下游基因的可能治疗靶点，从而为个性化医学设计有效的治疗策略。
