长链非编码RNA DMTF1v4在结肠癌发生中的分子机制  

Mechanism of Long Non–coding RNA DMTF1v4 in the Occurrence of Colon Cancer

作　　者：蔡燕娟[1] 庄树彤[1] 曾理[1] 刘鸿鹏 邱建夫 陈斌[1] CAI Yan-juan;ZHUANG Shu-tong;ZENG Li;LIU Hong-peng;QIU Jian-fu;CHEN Bin(Shenzhen Second People＇s Hospital,The First Affiliated Hospital of Shenzhen University,Guangdong Shenzhen 518035)

机构地区：[1]深圳市第二人民医院深圳大学第一附属医院,广东深圳518035

出　　处：《深圳中西医结合杂志》2018年第19期1-5,共5页Shenzhen Journal of Integrated Traditional Chinese and Western Medicine

基　　金：深圳市卫生计生系统科研项目资助课题(201601024;201601021)

摘　　要：目的:探讨长链非编码RNA(lncRNA)DMTF1v4在结肠癌中的表达情况,并研究其表达量与结肠癌发生的关系。方法:分别取2016年7月至2016年12月深圳市第二人民医院胃肠外科收治的结肠癌患者的结肠癌和癌旁组织,用半定量聚合酶链反应(PCR)检测lncRNA DMTF1v4表达;采用siRNA下调DMTF1v4在结肠癌细胞株HT–29中的表达,通过噻唑兰(MTT)检测和平板克隆实验研究沉默DMTF1v4对结肠癌细胞生长的影响;通过AnnexinV/PI双染法检测DMTF1v4对结肠癌细胞凋亡的影响;应用免疫印迹检测蛋白p–ERK、p–JNK和p–p38的变化;采用沉默DMTF1v4的HT–29构建裸鼠皮下异位移植瘤模型,研究其在动物体内对肿瘤生长的影响。结果:lncRNA DMTF1v4在结肠癌组织中的表达明显高于癌旁组织,差异具有统计学意义(P <0.01);采用lncRNA DMTF1v4低表达的细胞系研究,结果表明lncRNA DMTF1v4有促进细胞增殖和迁移并抑制细胞凋亡的作用,差异具有统计学意义(P <0.05);研究lncRNA DMTF1v4对ERK/MAPK信号通路的影响,通过沉默DMTF1v4发现其p–ERK、p–JNK和p–p38的表达明显增加,差异具有统计学意义(P <0.01);研究沉默基因DMTF1v4在动物体内对肿瘤生长的影响,发现裸鼠肿瘤的增长受到抑制,凋亡相关蛋白的表达增加,差异具有统计学意义(P <0.01)。结论:lncRNA DMTF1v4在结肠癌组织中的表达明显高于癌旁组织;lncRNA DMTF1v4通过下调蛋白p–ERK、p–JNK和p–p38的表达进而促进结肠癌细胞增殖和迁移,抑制凋亡,从而影响结肠癌的发展。这将为临床治疗结肠癌提供新思路。Objective To investigate the expression of long non–coding RNA（lncRNA） DMTF1 v4 in colon cancer, and the relationship between its expression and disease occurrence. Methods Human colon cancer tissues and para-carcinoma tissues were harvested. The expression of lncRNA DMTF1 v4 was measured by semi-quantitative PCR. The expression of DMTF1 v4 in HT–29 colon cancer cells was downregulated using siRNA, and the effect of its downregulation on cell growth was determined by MTT assay and plate clone assay. The effect of DMTF1 v4 downregulation on colon cancer cell migration was determined using a transwell assay and scratch wound assay. The effect of DMTF1 v4 on colon cancer cell apoptosis was determined using Annexin V/PI double–staining. The changes in p–ERK, p–JNK, and p–p38 were measured by Western blot. HT– 29 cells with downregulated DMTF1 v4 expression were used to establish the subcutaneous heterotopic transplantation tumor model in nude mice to study the effect of DMTF1 v4 on tumor growth in animals. Results Compared with para–carcinoma tissue, lncRNA DMTF1 v4 in colon cancer tissue was highly expressed（P〈0.01）. Downregulating lncRNA DMTF1 v4 in HT–29 cells showed that lncRNA DMTF1 v4 promotes cell proliferation, and suppresses apoptosis（P〈0.05）. The effect of lncRNA DMTF1 v4 on the ERK/MAPK signaling pathway was evaluated. The expression of p–ERK, p–JNK, and p–p38 was increased significantly compared with the control group（P〈0.01）. The effect of downregulating DMTF1 v4 on tumor growth in animals showed that tumor growth in nude mice was decreased, and the expression of apoptosis–Related proteins was increased（P〈0.01）. Conclusion The expression of lncRNA DMTF1 v4 is elevated in colon cancer tissues; lncRNA DMTF1 v4 promotes colon cancer cell proliferation, and inhibits apoptosis by downregulating the expression of p–ERK, p–JNK, and p–p38, thus affecting the progression of colon cancer. This will provide a basis for the development of new clinical treat

关 键 词：长链非编码RNA DMTF1v4 结肠癌 ERK/MAPK信号通路 

分 类 号：R735.35[医药卫生—肿瘤]