Oncogenic Role of EEPD1 via Protein Kinase B Phosphorylation in Colorectal Cancer

Abstract

Introduction: Endonuclease/exonuclease/phosphatase family domain-containing 1 (EEPD1) is involved in deoxyribonucleic acid (DNA) repair and promotes the repair of oxidative-stressed replication forks. This study explored the oncological importance of EEPD1 in colorectal cancer (CRC).

Methods: We first evaluated the levels of EEPD1 mRNA by reverse transcription-quantitative polymerase chain reaction (PCR) and of EEPD1 protein by immunohistochemistry in samples from 289 CRC patients. We then investigated the cancer-promoting function of EEPD1 by performing a series of in vitro assays in CRC cells (SW620 and WiDr) to assess cell proliferation, migration, apoptosis, and signal transduction.

Results: We revealed that the mRNA and protein levels of EEPD1 were remarkably higher in tumor tissues than in adjacent normal mucosa. Furthermore, patients with high levels of EEPD1 showed significantly poorer overall survival (P = 0.0001) and recurrence-free survival (P = 0.046). Moreover, siRNA knockdown of EEPD1 significantly inhibited cell proliferation (P < 0.05) and migration activity (P < 0.05), enhanced apoptotic activity (P < 0.05), and reduced phosphorylation of protein kinase B (AKT) in SW620 and WiDr CRC cells (P < 0.05).

Conclusions: EEPD1 is a promising prognostic and recurrence-predictive biomarker in CRC patients and is a potential therapeutic target in CRC.

Keywords: Biomarker; Colorectal cancer; EEPD1; Protein kinase B.