Yang Haiyan, Liu Zhenguo, Yuan Cuncun, Zhao Yunfei, Wang Lei, Hu Jiong, Xie Dacheng, Wang Liwei, Chen Donghui
Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 201620, China ; Shanghai Key Laboratory of Pancreatic Diseases Shanghai 201620, China.
Department of Anesthesiology, Weifang People's Hospital 151 Guang Wen Street, Weifang 261041, Shandong, China.
Int J Clin Exp Pathol. 2015 Sep 1;8(9):11092-9. eCollection 2015.
Jumonji domain-containing protein 1A (JMJD1A) play a key role in the development and progression of several malignancies. The present study investigated the expression and clinical significance of JMJD1A in gastric cancer. JMJD1A was found to be upregulated in gastric cancer tissues and cell lines. Furthermore, the upregulated expression of JMJD1A was significantly correlated with the results of the invasion depth (P=0.006), lymph node metastatic status (P<0.001), and TNM stage (P<0.001). JMJD1A was also shown to be an independent prognostic predictor of overall survival (HR3.988; 95% CI 1.948-8.167; P<0.001) for patients with gastric cancer. In addition, in vitro experiment revealed that knockdown of JMJD1A expression inhibited the gastric cancer cell proliferation, and further study suggested that JMJD1A knockdown suppressed MAPK pathway via transcriptional downregulation the expression of long noncoding RNA MALAT1. Therefore, we speculated that JMJD1A-MALAT1-MAPK signaling might participate in the JMJD1A-induced cell proliferation of gastric cancer. Collectively, our data demonstrate for the first time that JMJD1A gene has an important regulatory role in gastric carcinogenesis, and could function as a novel prognostic indicator and a potential therapeutic target for gastric cancer.
含Jumonji结构域蛋白1A（JMJD1A）在多种恶性肿瘤的发生和发展中起关键作用。本研究调查了JMJD1A在胃癌中的表达及临床意义。发现JMJD1A在胃癌组织和细胞系中上调。此外，JMJD1A的上调表达与浸润深度结果（P = 0.006）、淋巴结转移状态（P < 0.001）和TNM分期（P < 0.001）显著相关。JMJD1A还被证明是胃癌患者总生存的独立预后预测指标（HR 3.988；95% CI 1.948 - 8.167；P < 0.001）。此外，体外实验显示敲低JMJD1A表达可抑制胃癌细胞增殖，进一步研究表明敲低JMJD1A通过转录下调长链非编码RNA MALAT1的表达抑制MAPK通路。因此，我们推测JMJD1A - MALAT1 - MAPK信号通路可能参与JMJD1A诱导的胃癌细胞增殖。总体而言，我们的数据首次证明JMJD1A基因在胃癌发生中具有重要调控作用，并可作为胃癌的新型预后指标和潜在治疗靶点。
