Peng Yun-Peng, Zhu Yi, Yin Ling-Di, Zhang Jing-Jing, Wei Ji-Shu, Liu Xian, Liu Xin-Chun, Gao Wen-Tao, Jiang Kui-Rong, Miao Yi
Pancreas Center, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, People's Republic of China.
Pancreas Institute, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China.
J Exp Clin Cancer Res. 2017 Feb 13;36(1):30. doi: 10.1186/s13046-017-0500-x.
Overexpression of paternally expressed gene-10 (PEG10) is known to promote the progression of several carcinomas, however, its role in pancreatic cancer (PC) is unknown. We investigated the expression and function of PEG10 in PC.
PEG10 expression and correlation with PC progression was assessed in cancerous tissues and paired non-cancerous tissues. Further, the role of PEG10 in PC cell progression and the underlying mechanisms were studied by using small interfering RNA (Si-RNA).
PEG10 expression was significantly higher in cancerous tissues and correlated with PC invasion of vessels and Ki-67 expression. Si-RNA mediated PEG10 knockdown resulted in inhibition of proliferation and G0/G1 cell cycle arrest, which was mediated by p21 and p27 upregulation. A decrease in PC cell invasion and migration, mediated by ERK/MMP7 pathway, was observed in PEG10 knockdown group. Further, findings of ChIP assay suggested that E2F-1 could directly enhance the expression of PEG10 through binding to PEG10 promoter.
In conclusion, PEG10 was identified as a prognostic biomarker for PC and E2F-1 induced PEG10 could promote PC cell proliferation, invasion, and metastasis.
已知父源表达基因10(PEG10)的过表达会促进多种癌症的进展,然而,其在胰腺癌(PC)中的作用尚不清楚。我们研究了PEG10在PC中的表达及功能。
评估癌组织和配对的非癌组织中PEG10的表达及其与PC进展的相关性。此外,通过使用小干扰RNA(Si-RNA)研究PEG10在PC细胞进展中的作用及其潜在机制。
癌组织中PEG10表达显著更高,且与PC的血管浸润和Ki-67表达相关。Si-RNA介导的PEG10敲低导致增殖抑制和G0/G1期细胞周期阻滞,这是由p21和p27上调介导的。在PEG10敲低组中观察到由ERK/MMP7途径介导的PC细胞侵袭和迁移减少。此外,染色质免疫沉淀实验结果表明,E2F-1可通过与PEG10启动子结合直接增强PEG10的表达。
总之,PEG10被确定为PC的预后生物标志物,且E2F-1诱导的PEG10可促进PC细胞增殖、侵袭和转移。