Lin Wei-Tung, Shieh Tzong-Ming, Yang Li-Chiu, Wang Tung-Yuan, Chou Ming-Yung, Yu Cheng-Chia
Division of Nephrology, Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan.
Department of Dental Hygiene, College of Health Care, China Medical University, Taichung, Taiwan.
J Oral Pathol Med. 2015 Nov;44(10):823-30. doi: 10.1111/jop.12314. Epub 2015 Feb 27.
Lymph node (LN) metastasis is the most common cause of oral squamous cell carcinoma (OSCC)-related death. Searching the detailed molecular mechanisms involved LN metastasis in OSCC is still an open question.
Paired tissue samples from tumor (T) and adjacent non-cancerous matched tissues (NCMT) parts, as well as LN metastatic lesions in patient with OSCC tissues were subjected to quantitative real-time PCR analysis for the expression levels of Lin28B. Arecoline, a major areca nut alkaloid, was to explore whether expression of Lin28B could be changed dose dependent in oral epithelial cells. Control and Lin28B-knockdown arecoline-stimulated oral epithelial cells were subjected to migration/invasion/anchorage-independent growth assay.
Compared with NCMT samples from the same OSCC patient, the expression of Lin28B was increased in all of the tumor samples. A similar upregulation of Lin28B was also observed in LN metastatic when compared with local tumors. Arecoline treatment dose dependently induced Lin28B expression in SG and FaDu cells. Lentiviral-mediated silencing Lin28B expression significantly attenuated arecoline-induced oncogenicity including proliferation, migration, invasiveness, and anchorage-independent growth in SG and FaDu cells.
Lin28B may be a useful biomarker and novel molecular target for LN metastasis OSCC patients' treatment.
淋巴结转移是口腔鳞状细胞癌(OSCC)相关死亡的最常见原因。探寻OSCC中涉及淋巴结转移的详细分子机制仍是一个悬而未决的问题。
对来自肿瘤(T)和相邻非癌匹配组织(NCMT)部位的配对组织样本,以及OSCC患者组织中的淋巴结转移病变进行定量实时PCR分析,以检测Lin28B的表达水平。槟榔碱是槟榔的主要生物碱,旨在探究在口腔上皮细胞中Lin28B的表达是否会随剂量依赖性变化。对对照和Lin28B敲低的槟榔碱刺激的口腔上皮细胞进行迁移/侵袭/非锚定依赖性生长分析。
与同一OSCC患者的NCMT样本相比,所有肿瘤样本中Lin28B的表达均增加。与局部肿瘤相比,在淋巴结转移中也观察到类似的Lin28B上调。槟榔碱处理在SG和FaDu细胞中剂量依赖性地诱导Lin28B表达。慢病毒介导的Lin28B表达沉默显著减弱了槟榔碱诱导的致癌性,包括SG和FaDu细胞中的增殖、迁移、侵袭性和非锚定依赖性生长。
Lin28B可能是OSCC患者淋巴结转移治疗的有用生物标志物和新分子靶点。