Overexpressed PLAGL2 transcriptionally activates Wnt6 and promotes cancer development in colorectal cancer
Overexpressed PLAGL2 transcriptionally activates Wnt6 and promotes cancer development in colorectal cancer
复制标题
过表达的 PLAGL2 转录激活 Wnt6 并促进结直肠癌的发展
DOI：
10.3892/or.2018.6914
复制
发表时间：
2019-02-01
期刊：
影响因子：
4.2
通讯作者：
Hu, Gui
中科院分区：
文献类型：
--
作者：
Li, Nanpeng;Li, Daojiang;Hu, Gui
研究人员认为PLAGL 2在许多恶性肿瘤中过表达，并可促进肿瘤增殖、迁移、侵袭和自我更新;但没有证据表明PLAGL 2与结直肠癌（CRC）之间存在关系。本研究利用COSMIC数据库和GEPIA数据库筛选大肠癌中过表达的基因，并采用RT-qPCR和western blot检测大肠癌组织和癌旁组织中PLAGL 2的表达。采用Cell Counting Kit-8法、细胞周期分析实验和异种移植模型研究PLAGL 2在HCT 116和SW 480细胞中敲低表达后对CRC的影响。使用ChIP测定和双荧光素酶报告基因测定，发现PLAGL 2结合的启动子区域。据观察，PLAGL 2在结直肠癌中过表达，并且其影响结直肠癌细胞周期并促进体内和体外结直肠癌增殖。在敲低PLAGL 2表达后，Wnt/β-catenin通路中的一些基因的表达下调; Wnt 6的变化最大。PLAGL 2可与Wnt 6的启动子区结合，促进Wnt 6的表达。这些结果表明PLAGL 2作为原癌基因在CRC中过表达，并且它可以作为转录因子通过与Wnt 6的启动子区域结合来激活Wnt/β-catenin途径。PALGL 2在结直肠癌中发挥重要作用，有望成为靶向药物治疗的新靶点。
Researchers hold the view that PLAGL2 is overexpressed in many malignancies and that it can promote tumor proliferation, migration, invasion and self-renewal; however, there is no evidence revealing a relationship between PLAGL2 and colorectal cancer (CRC). In the present study, genes that are overexpressed in CRC were screened using the COSMIC database and GEPIA database and the expression of PLAGL2 in carcinoma tissues and pericarcinomatous tissues was detected by RT-qPCR and western blot assays. A Cell Counting Kit-8 assay, a cell cycle analysis experiment and a xenograft model were used to explore the influence of PLAGL2 on CRC after knocking down PLAGL2 expression in HCT116 and SW480 cells. Using ChIP assays and Dual-Luciferase Reporter assays, the promoter regions to which PLAGL2 binds were discovered. It was observed that PLAGL2 was overexpressed in colorectal cancer and that it influenced the colorectal cancer cell cycle and promoted colorectal cancer proliferation in vivo and in vitro. The expression of some genes in the Wnt/β-catenin pathway, were downregulated after knocking down the expression of PLAGL2; Wnt6 was altered the most. PLAGL2 could bind to the promoter region of Wnt6 and promote its expression. These results indicated that PLAGL2 was overexpressed in CRC as a proto-oncogene and that it could active the Wnt/β-catenin pathway as a transcription factor by binding with the promoter region of Wnt6. PALGL2 was revealed to play an important role in colorectal cancer and may be a new therapeutic target for targeted medicine.