Li Xin, Gao Shuhong, Li Wenzhi, Liu Zhiming, Shi Zhengzheng, Qiu Chunping, Jiang Jie
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
Department of Obstetrics and Gynecology, Zaozhuang Municipal Hospital, Zaozhuang, China.
J Obstet Gynaecol Res. 2019 Oct;45(10):2043-2054. doi: 10.1111/jog.14070. Epub 2019 Jul 29.
Abnormal lipid metabolism plays a dual role in tumorigenesis, specifically in the occurrence and development of cancers. Monoacylglycerol lipase (MAGL), a hydrolase that is important for lipid metabolism, plays a vital role in different aspects of tumorigenesis. Many studies have shown that MAGL is highly elevated in a variety of cancers and plays an active role. However, its potential role in supporting endometrial cancer (EC) growth and progression has not yet been explored in depth.
Immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction were performed to estimate the protein and messenger RNA (mRNA) levels of MAGL in tumor tissues. Then, JZL184 and small interfering RNA (siRNA) were used to decrease the expression of MAGL in EC cells. The gene and protein expression levels of MAGL were measured using quantitative real-time PCR and western blotting, respectively. Additionally, the effect of MAGL on tumor growth in EC was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide , cell cycle and western blotting assay in vitro.
We found that MAGL was overexpressed in EC and was significantly correlated with surgical-pathological stage, myometrial invasion, number of pregnancies and body mass index. The growth and cell cycle progression of tumor cells were significantly impaired in vitro by the pharmacological and siRNA-mediated MAGL inhibition. In addition, MAGL inhibition seemed to repress two target genes, Cyclin D1 and Bcl-2.
In summary, we have demonstrated that MAGL is involved in EC growth and progression. Our results suggest that targeting MAGL may be a novel and valid treatment for EC.
脂质代谢异常在肿瘤发生过程中起双重作用,特别是在癌症的发生和发展中。单酰甘油脂肪酶(MAGL)是一种对脂质代谢很重要的水解酶,在肿瘤发生的不同方面起着至关重要的作用。许多研究表明,MAGL在多种癌症中高度升高并发挥积极作用。然而,其在支持子宫内膜癌(EC)生长和进展方面的潜在作用尚未得到深入研究。
采用免疫组织化学和定量实时逆转录聚合酶链反应来估计肿瘤组织中MAGL的蛋白质和信使核糖核酸(mRNA)水平。然后,使用JZL184和小干扰RNA(siRNA)来降低EC细胞中MAGL的表达。分别使用定量实时聚合酶链反应和蛋白质印迹法测量MAGL的基因和蛋白质表达水平。此外,通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐、细胞周期和蛋白质印迹分析在体外检测MAGL对EC肿瘤生长的影响。
我们发现MAGL在EC中过表达,并且与手术病理分期、肌层浸润、妊娠次数和体重指数显著相关。药理学和siRNA介导的MAGL抑制在体外显著损害了肿瘤细胞的生长和细胞周期进程。此外,MAGL抑制似乎抑制了两个靶基因,细胞周期蛋白D1和Bcl-2。
总之,我们已经证明MAGL参与了EC的生长和进展。我们的结果表明,靶向MAGL可能是一种新型且有效的EC治疗方法。