Methylation and Expression Status of SOCS 1 and SOCS 3 in Oral Lichen Planus
Methylation and Expression Status of SOCS 1 and SOCS 3 in Oral Lichen Planus
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DOI：
10.4236/ojst.2018.85016
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发表时间：
2018-05
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影响因子：
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通讯作者：
K. Yoshimura;N. Yada;K. Matsuo;H. Hikiji;D. Yoshiga;M. Habu;M. Sasaguri;K. Tominaga
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作者：
K. Yoshimura;N. Yada;K. Matsuo;H. Hikiji;D. Yoshiga;M. Habu;M. Sasaguri;K. Tominaga
口腔扁平苔藓（OLP）是一种病因不明的疾病，通过介导的慢性炎症影响口腔粘膜，并被归类为潜在的恶性口腔疾病。SOCS家族中的SOCS 1和SOCS 3已被鉴定为负责炎症反应的丝氨酸激活的JAK/STAT通路的负调节剂。SOCS 1和SOCS 3基因启动子区的甲基化与肿瘤的发生有关。在这项研究中，我们进行了甲基化特异性PCR（MSP），以调查SOCS 1和SOCS 3基因的启动子区域的甲基化状态使用活检样本OLP和口腔鳞状细胞癌（OSCC）患者。OLP组SOCS 1基因甲基化阳性率为48.3%（14/29），OSCC组SOCS 1基因甲基化阳性率为46.7%（7/15）。OLP组SOCS 3甲基化阳性率为86.2%（25/29），OSCC组为73.3%（11/15）。在正常颊粘膜脱落细胞学标本中未发现SOCS 1和SOCS 3基因的甲基化。采用实时荧光定量RT-PCR方法分析mRNA表达水平与DNA甲基化状态的相关性。SOCS 1基因的甲基化状态对SOCS 1 mRNA的表达水平无明显影响。SOCS 3基因甲基化状态与SOCS 3 mRNA表达水平呈负相关（p < 0.05）。SOCS 3基因启动子区频繁甲基化可能与OLP的发病机制有关，从理论上讲，SOCS 3基因启动子区甲基化可导致细胞因子表达增加。
Oral lichen planus (OLP) is a disease of unknown etiology affecting oral mucosa by mediated chronic inflammation and is classified as a potentially malignant oral disorder. SOCS1 and SOCS3 in the SOCS family have been identified as negative regulators of the cytokine-activated JAK/STAT pathway responsible for inflammatory reaction. The DNA methylation in the promoter regions of SOCS1 and SOCS3 have been reported to correlate with carcinogenesis. In this study, we performed methylation-specific PCR (MSP) to investigate the methylation status of the promoter regions in SOCS1 and SOCS3 genes using biopsy samples from OLP and oral squamous cell carcinoma (OSCC) patients. SOCS1 was methylated in 14/29 (48.3%) cases with OLP and 7/15 (46.7%) cases with OSCC. At the same time, SOCS3 was methylated in 25/29 (86.2%) cases with OLP and 11/15 (73.3%) cases with OSCC. We didn’t recognize any DNA methylation in SOCS1 or SOCS3 genes from the exfoliated cytological specimens of normal buccal mucosa. Furthermore, mRNA expression level was analyzed using real-time RT-PCR method to evaluate the correlation with DNA methylation status. DNA methylation status of SOCS1 seemed not to affect the expression level of SOCS1 mRNA. At the same time, DNA methylation status of SOCS3 was negatively correlated with the expression level of SOCS3 mRNA (p < 0.05). We posit frequent methylation of the SOCS3 gene promoter, theoretically resulting in the increase of cytokines expression, might be associated with the etiological mechanism of OLP.