Abstract
BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most frequent malignant tumors originated from digestive system around the world and the treatment was limited by the unclear mechanism. DNA polymerase epsilon 2, accessory subunit (POLE2) is involved in DNA replication, repair, and cell cycle control, whose association with ESCC is still not clear.MethodsIn this study, the expression level of POLE2 in ESCC tissues was detected by IHC. The POLE2 knockdown cell line was constructed, identified by qPCR and western blot and used for detecting cellular functions and constructing xenotransplantation mice model. MTT Assay, colony formation assay, flow cytometry, wound-healing assay and Transwell assay were used to detected cell proliferation, apoptosis and migration.ResultsWe firstly identified that the expression of POLE2 was overexpressed in ESCC. Moreover, the high expression of POLE2 can predict the tumor deterioration and poor prognosis of ESCC patients. Additionally, downregulation of POLE2 was involved in ESCC progression by promoting proliferation, migration, and inhibiting apoptosis in vitro. In vivo studies proved that POLE2 was positively correlated with ESCC tumor formation, which was consistent with the results in vitro. We also illuminated that POLE2 knockdown upregulated pro-apoptotic proteins (Bax, Caspase3, CD40L, FasL, IGFBP-5 and P21) and downregulated anti-apoptotic proteins (CLAP-2, IGF-I and sTNF-R2). In addition, POLE2 was involved in ESCC via targeting PI3K/Akt, Cyclin D1 signaling pathway.ConclusionsTherefore, POLE2 was proved to be involved in the development of ESCC, which may be a potential therapeutic target and bring new breakthroughs in the treatment of ESCC.
Highlights
Esophageal cancer (EC) is one of the most aggressive gastrointestinal cancers in the world [1]
In vivo studies proved that POLE2 was positively correlated with Esophageal squamous cell carcinoma (ESCC) tumor formation, which was consistent with the results in vitro
The number of clinical specimens included in this study is small and the underlying mechanism of POLE2 mediated regulation of ESCC is still not clear
Summary
Esophageal cancer (EC) is one of the most aggressive gastrointestinal cancers in the world [1]. Esophageal squamous cell carcinoma (ESCC) is one of the main subtypes of EC. The comprehensive treatment ESCC consists of surgery and definitive chemoradiotherapy, supplemented with cisplatin and 5-fluorouracil (5-FU) (CF) [3]. It was reported that agents inhibiting erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2), and vascular endothelial growth factor (VEGF), such as Trastuzumab, Ramucirumab and Lapatinib, could improve survival of ESCC patients [4]. The treatments of ESCC could only relieve symptoms, but the prognosis is still poor, especially with a 5-year survival rate of less than 40% [5, 6]. Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignant tumors originated from digestive system around the world and the treatment was limited by the unclear mechanism. DNA polymerase epsilon 2, accessory subunit (POLE2) is involved in DNA replication, repair, and cell cycle control, whose association with ESCC is still not clear
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