Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
Oncol Rep. 2019 Feb;41(2):875-884. doi: 10.3892/or.2018.6914. Epub 2018 Dec 7.
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.
研究人员认为，PLAGL2 在许多恶性肿瘤中过度表达，可促进肿瘤增殖、迁移、侵袭和自我更新；然而，尚无证据表明 PLAGL2 与结直肠癌（CRC）之间存在关联。在本研究中，使用 COSMIC 数据库和 GEPIA 数据库筛选 CRC 中过度表达的基因，并通过 RT-qPCR 和 Western blot 检测癌组织和癌旁组织中 PLAGL2 的表达。通过细胞计数试剂盒-8 检测、细胞周期分析实验和异种移植模型，在 HCT116 和 SW480 细胞中敲低 PLAGL2 表达后，研究了 PLAGL2 对 CRC 的影响。通过 ChIP 检测和双荧光素酶报告基因检测，发现了 PLAGL2 结合的启动子区域。结果表明，PLAGL2 在结直肠癌中过表达，影响结直肠癌细胞周期，并促进结直肠癌在体内和体外的增殖。敲低 PLAGL2 表达后，Wnt/β-catenin 通路中的一些基因表达下调；Wnt6 的变化最为明显。PLAGL2 可结合 Wnt6 的启动子区域并促进其表达。这些结果表明，PLAGL2 作为原癌基因在 CRC 中过表达，并可通过与 Wnt6 的启动子区域结合作为转录因子激活 Wnt/β-catenin 通路。PLAGL2 在结直肠癌中发挥重要作用，可能成为靶向药物的新治疗靶点。
