我國(guó)是胃癌的高發(fā)區(qū),，每年新發(fā)現(xiàn)約40萬(wàn)胃癌患者，占世界胃癌發(fā)病人數(shù)的40%左右,。我國(guó)胃癌死亡率是歐美發(fā)達(dá)國(guó)家的4-8倍,，是當(dāng)前危害人民身體健康的重大疾病。幽門螺旋桿菌感染,，生活中情緒壓力,，不良的飲食習(xí)慣，如喜好熏烤,、高鹽,、辛辣食物及酗酒，都會(huì)破壞和損傷胃粘膜,，造成胃炎,、胃潰瘍等疾病，導(dǎo)致胃癌發(fā)生的高風(fēng)險(xiǎn),。蛋白酶激活受體4（Protease-Activated Receptor 4, PAR4）廣泛表達(dá)于胃粘膜中,，其在胃粘膜保護(hù)和損傷修復(fù)、胃癌發(fā)生中的作用是待解決的科學(xué)問(wèn)題,。
中科院昆明動(dòng)物研究所動(dòng)物模型與人類疾病機(jī)理重點(diǎn)實(shí)驗(yàn)室生物毒素與人類疾病課題組在張?jiān)蒲芯繂T帶領(lǐng)下,，該課題組張勇和余國(guó)宇博士等在揭示蛋白酶激活受體可作為胃粘膜損傷修復(fù)三葉因子的細(xì)胞膜受體基礎(chǔ)上（Cell Mol Life Sci. 2011 Apr 3），進(jìn)一步與昆明醫(yī)學(xué)院第一附屬醫(yī)院合作,，采用分子生物學(xué),、細(xì)胞生物學(xué)和臨床病理學(xué)研究技術(shù)發(fā)現(xiàn)該粘膜損傷修復(fù)的“中介”（PAR4受體）在胃癌病人中顯著性下降，其缺失與胃癌的淋巴結(jié)轉(zhuǎn)移,、低分化程度相關(guān),；PAR4受體基因啟動(dòng)區(qū)超甲基化是引起該受體表達(dá)缺失的主要原因，揭示不良生活習(xí)慣和環(huán)境因素等在胃癌發(fā)生中的重要作用,。
文章已在線發(fā)表于《國(guó)際生物化學(xué)與細(xì)胞生物學(xué)期刊》（International Journal of Biochemistry and Cell biology） ,。上述結(jié)果為深入解析人胃粘膜保護(hù)、損傷修復(fù)和胃癌發(fā)生的生理病理機(jī)制提供了新的視角和線索,，也為臨床胃癌病理進(jìn)程及預(yù)后檢測(cè)提供了新的可能性,。
該研究受到國(guó)家973計(jì)劃項(xiàng)目、國(guó)家基金委重點(diǎn)項(xiàng)目以及中國(guó)科學(xué)院重要方向項(xiàng)目的資助,。（生物谷Bioon.com）
專題：MicroRNA 和 癌癥
生物谷推薦原文出處：
Journal of Biochemistry and Cell biology DOI： 10.1016/j.biocel.2011.05.008
Decreased expression of protease-activated receptor 4 in human gastric cancer
Yong Zhang, Guoyu Yu, Ping Jiang, Yang Xiang, Wenliang Li, Wenhui Lee and Yun Zhang
Protease-activated receptors (PARs) are a unique family of G-protein coupled receptors. PAR4, the most recently identified PAR member, was reported to be overexpressed during the progression of colon and prostate cancers. Though PAR4 mRNA was detected in normal stomach, the role of PAR4 in gastric cancer has not been investigated. In this study, differential expression of PAR4 was measured by real-time PCR (n = 28) and tissue microarrays (n = 74). We showed that PAR4 was located from basal to middle portions of normal gastric mucosa. PAR4 expression was remarkably decreased in gastric cancer tissues as compared with matched noncancerous tissues, especially in positive lymph node or low differentiation cancers. Furthermore, methylation of the PAR4 promoter in cell lines was assessed by treatment with 5-aza-2′-deoxycytidine and genomic bisulfite sequencing. AGS and N87 human gastric cancer cell lines did not express PAR4, as compared to HT-29 human colon cancer cell line with significant PAR4 expression. Treatment with 5-aza-2′-deoxycytidine restored PAR4 expression in AGS and N87 cells, which exhibited significantly more 5-methylcytosines in the PAR4 promoter compared with HT-29 cells. Our results revealed that down-regulation of PAR4 expression occurs frequently in gastric cancers and exhibits association with more aggressive gastric cancer. Interestingly, the loss of PAR4 expression in gastric cancers may result from hypermethylation of the PAR4 promoter.
