E2A predicts prognosis of colorectal cancer patients and regulates cancer cell growth by targeting miR-320a.
OBJECTIVE
Transcriptional 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.


METHODS
E2A 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.


RESULTS
Expression 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.


CONCLUSIONS
E2A is an independent prognostic factor for CRC patients and targets miR-320a to regulate cell proliferation of colon cancer cells.
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China ; Shanghai Institute of Digestive Surgery, Shanghai, China ; Shanghai Minimally Invasive Surgery Center, Shanghai, China.
Ao
A
Huang
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China ; Shanghai Institute of Digestive Surgery, Shanghai, China ; Shanghai Minimally Invasive Surgery Center, Shanghai, China.
Hongchao
H
Zhao
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China ; Shanghai Institute of Digestive Surgery, Shanghai, China ; Shanghai Minimally Invasive Surgery Center, Shanghai, China.
Yingjun
Y
Quan
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China ; Shanghai Institute of Digestive Surgery, Shanghai, China ; Shanghai Minimally Invasive Surgery Center, Shanghai, China.
Runsen
R
Jin
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China ; Shanghai Institute of Digestive Surgery, Shanghai, China ; Shanghai Minimally Invasive Surgery Center, Shanghai, China.
Bo
B
Feng
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China ; Shanghai Institute of Digestive Surgery, Shanghai, China ; Shanghai Minimally Invasive Surgery Center, Shanghai, China.
Minhua
M
Zheng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D003710:Demography; D018572:Disease-Free Survival; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models
D051792:Basic Helix-Loop-Helix Proteins; D035683:MicroRNAs; C572916:MIRN320 microRNA, human; C407909:TCF3 protein, human