Down-regulation of interferon regulatory factor 2 binding protein 2 suppresses gastric cancer progression by negatively regulating connective tissue growth factor
Down-regulation of interferon regulatory factor 2 binding protein 2 suppresses gastric cancer progression by negatively regulating connective tissue growth factor
复制标题
下调干扰素调节因子 2 结合蛋白 2 通过负向调节结缔组织生长因子抑制胃癌进展
DOI：
10.1111/jcmm.14677
复制
发表时间：
2019-09-27
影响因子：
5.3
通讯作者：
Deng, Jun
中科院分区：
文献类型：
--
作者：
Yao, Yangyang;Wang, Yi;Deng, Jun
干扰素调节因子2结合蛋白2（IRF 2BP 2）是一种转录抑制因子，参与调节基因表达和其他生物学过程，包括肿瘤发生。然而，IRF 2BP 2在人胃癌（GC）中的临床意义和作用仍不确定。临床胃癌组织取自南昌大学第一附属医院胃癌患者。免疫组化法检测临床石蜡标本中IRF 2BP 2蛋白的表达。MTT法、集落形成实验和transwell实验检测细胞增殖、迁移和侵袭能力。采用免疫共沉淀法检测TEA结构域家族成员4（TEAD 4）与VGLL 4或YAP 1之间的相互作用。使用双荧光素酶报告基因测定来确认miR-101- 3 p与3 '-UTR的结合。IRF 2BP 2在胃癌组织中的表达显著高于正常组织。IRF 2BP 2蛋白高表达的患者生存率较低。IRF 2BP 2基因敲低可抑制胃癌细胞的增殖、迁移、侵袭和上皮-间质转化。IRF 2BP 2敲低降低结缔组织生长因子（CTGF）的mRNA和蛋白水平。IRF 2BP 2和VGLL 4之间的相互作用增加了TEAD 4与YAP 1的结合，导致CTGF的转录共激活。此外，miR-101- 3 p通过直接靶向IRF 2BP 2的3 '-UTR抑制CTGF的表达。综上所述，这些发现为miR-101- 3 p-IRF 2BP 2-CTGF信号传导轴在GC中的作用提供了模型，并为GC进展和转移的机制提供了新的见解。
Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional repressor involved in regulating gene expression and other biological processes, including tumorigenesis. However, the clinical significance and roles of IRF2BP2 in human gastric cancer (GC) remain uncertain. Clinical GC tissues were obtained from GC patients at the First Affiliated Hospital of Nanchang University. Immunohistochemistry (IHC) was conducted to detect the IRF2BP2 protein in clinical paraffin specimens. Cell proliferation, migration and invasion were evaluated by MTT, colony formation assays and transwell assays. Co-immunoprecipitation was conducted to detect the interaction between TEA domain family members 4 (TEAD4) and vestigial-like family member 4 (VGLL4) or Yes-associated protein 1 (YAP1). Dual-luciferase reporter assay was used to confirm the binding of miR-101-3p to the 3 '-UTR. The expression of IRF2BP2 was significantly higher in GC tissues than in normal tissues. Patients with higher IRF2BP2 protein expression had lower survival. IRF2BP2 knockdown inhibited proliferation, migration, invasion and epithelial-mesenchymal transition in GC cells. IRF2BP2 knockdown decreased the mRNA and protein levels of connective tissue growth factor (CTGF). The interaction between IRF2BP2 and VGLL4 increased the binding of TEAD4 to YAP1, resulting in the transcriptional coactivation of CTGF. In addition, miR-101-3p suppressed the expression of CTGF by directly targeting the 3 '-UTR of IRF2BP2. Taken together, these findings provide a model for the role of miR-101-3p-IRF2BP2-CTGF signalling axis in GC and a novel insight into the mechanism of GC progression and metastasis.