Ladiz Mohammad Ayoub Rigi, Najafi Maryam, Kordi-Tamandani Dor Mohammad
Oral and dental disease research center, Zahedan University of Medical Science, Zahedan, Iran.
Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.
J Cell Commun Signal. 2017 Mar;11(1):49-55. doi: 10.1007/s12079-016-0356-4. Epub 2016 Oct 19.
The aberrant DNA methylation of the tumor suppressor genes involved in DNA Damage Response (DDR) signaling and cell cycle regulation may lead to the tumorigenesis. Our purpose here is to analyze the promoter methylation and mRNA expression levels of LATS1 and LATS2 (LATS1/2) genes in OSCC. Promoter methylation status of LATS1/2 genes was evaluated in 70 OSCC paraffin-embedded tissues and 70 normal oral samples, using Methylation Specific PCR (MSP). LATS1/2 mRNA expression profiles were also investigated in 14 OSCC patients and 14 normal samples, using real-time PCR. In both candidate genes, promoter methylation assessment revealed significant relationship between cases and controls (OR = 2.24, 95 % CI = 1.40-3.54, P = 0.001; LATS1 and OR = 15.5, 95%CI = 3.64-64.76, P < 0.001; LATS2). As well as, the evaluation of mRNA expression levels showed decreased expression in OSCC tissues in compare to control tissues. (Mean ± SD 1.74 ± 0.14 in OSCC versus 2.10 ± 0.24 in controls, P < 0.001; LATS1 and Mean ± SD 1.36 ± 0.077 in OSCC versus 1.96 ± 0.096 in controls, P < 0.001; LATS2). To the best our knowledge, this is the first report regarding the down-regulation of LATS1/2 through promoter methylation in OSCC. It is suggested to explore the down-stream transcription factors of both genes for finding the molecular mechanism of this deregulation in OSCC.
参与DNA损伤反应（DDR）信号传导和细胞周期调控的肿瘤抑制基因的异常DNA甲基化可能导致肿瘤发生。我们在此的目的是分析口腔鳞状细胞癌（OSCC）中LATS1和LATS2（LATS1/2）基因的启动子甲基化和mRNA表达水平。使用甲基化特异性PCR（MSP）在70例OSCC石蜡包埋组织和70例正常口腔样本中评估LATS1/2基因的启动子甲基化状态。还使用实时PCR在14例OSCC患者和14例正常样本中研究LATS1/2 mRNA表达谱。在两个候选基因中，启动子甲基化评估显示病例与对照之间存在显著关系（OR = 2.24，95%CI = 1.40 - 3.54，P = 0.001；LATS1，OR = 15.5，95%CI = 3.64 - 64.76，P < 0.001；LATS2）。此外，mRNA表达水平评估显示，与对照组织相比，OSCC组织中的表达降低。（OSCC中平均值±标准差为1.74±0.14，对照中为2.10±0.24，P < 0.001；LATS1，OSCC中平均值±标准差为1.36±0.077，对照中为1.96±0.096，P < 0.001；LATS2）。据我们所知，这是关于OSCC中通过启动子甲基化下调LATS1/2的首次报告。建议探索这两个基因的下游转录因子，以发现OSCC中这种失调的分子机制。
