Abstract
Background and objectiveTranscriptional factor E2A is crucial for the normal development and differentiation of B and T lymphocytes. Dysregulation of E2A leads to leukemia and tumorigenesis of some solid tumors. The expression and clinical significance of E2A as well as its role in colorectal cancer (CRC) are still unknown. This study aims to assess E2A expression in CRC tissues, evaluate its prognosis value, and investigate its role in colon cancer cell growth.MethodsE2A expression in CRC tissues and normal mucosa was detected by immunohistochemical staining; Kaplan-Meier survival curve and Cox regression model were used to evaluate the prognostic value of E2A. Lentivirus was used to construct E2A stably knocked-down cells. MTT assay was employed to detect cell proliferation change; cell cycle was analyzed by flow cytometry; and chromatin immunoprecipitation (ChIP) assay was used to validate the predicted binding target of E2A.ResultsExpression of E2A was lower in CRC tissues than normal mucosa; low E2A expression correlated with advanced TNM stage and larger tumor size, and predicted poor prognosis of CRC patients. E2A knockdown resulted in increased cell proliferation rate and cell cycle acceleration. ChIP assay showed miR-320a was a direct target of E2A and upregulation of miR-320a in E2A downregulated cells could reverse cell proliferation and cell cycle changes caused by E2A deficiency.ConclusionsE2A is an independent prognostic factor for CRC patients and targets miR-320a to regulate cell proliferation of colon cancer cells.
Highlights
The mammalian E2A gene is located at chromosome 19 and is non-tissue- and ubiquitously expressed in a wide range of cell types
Expression of E2A was lower in colorectal cancer (CRC) tissues than normal mucosa; low E2A expression correlated with advanced TNM stage and larger tumor size, and predicted poor prognosis of CRC patients
chromatin immunoprecipitation (ChIP) assay showed miR-320a was a direct target of E2A and upregulation of miR-320a in E2A downregulated cells could reverse cell proliferation and cell cycle changes caused by E2A deficiency
Summary
The mammalian E2A gene is located at chromosome 19 and is non-tissue- and ubiquitously expressed in a wide range of cell types. Studies had reported the well-established role of E2A in leukemogenesis: two fusion proteins, E2A-HLF [11] and E2A-PBX1 [12], both containing the transactivation domain of E2A and the DNA-binding domain of HLF or PBX1, could lead to pro-B cell acute lymphoblastic leukemia (ALL) in adolescents and pre-B cell ALL in children respectively [13]. E2A has been found to be involved in the oncogenesis of solid tumors, either as oncogene or as tumorsuppressor gene. Mice with null mutation of E2A were susceptible to spontaneously developed thymic lymphomas [18] and loss of E2A in primary effusion lymphoma led to apoptosis resistance [19], suggesting the alternative role of E2A as a tumorsuppressor gene. This study aims to assess E2A expression in CRC tissues, evaluate its prognosis value, and investigate its role in colon cancer cell growth
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