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Background  Although its biological function remains poorly understood, REG4 is reported to be a potent activator of the EGFR/Akt/AP-1 signaling pathway in colon cancer cells and closely linked with the inhibition of apoptosis.    Methods  SKOV3 cells were transfected with a REG4-expressing plasmid or treated with recombinant REG4. We then analyzed proliferation, cell cycle, apoptosis, invasion and metastasis or expression of related molecules.  REG4  expression was examined in normal ovarian tissue, benign and borderline tumors, and cancers by immunohistochemistry or real-time PCR.    Results  REG4 overexpression and the recombinant protein inhibited cell apoptosis, enhanced G 2 /S progression, proliferation, migration and invasion. Furthermore, expression of  Wnt5a ,  p70s6k, survivin  and  VEGF  expression was increased ,  while  Bax  expression was decreased at both the mRNA and protein levels compared to control or mock cells ( P  < 0.05).  REG4  mRNA levels were higher in benign tumors and primary cancer compared to those in normal ovarian tissue ( P  < 0.05) while, REG4 protein expression was higher in all three tumor types than that in normal ovarian tissue ( P  < 0.05). Higher REG4 mRNA expression was observed in mucinous carcinomas than serous carcinomas ( P  < 0.05), and in well- and moderately-differentiated carcinomas than poorly-differentiated carcinomas ( P  < 0.05). Survival analysis revealed an inverse relationship between REG4 expression and cumulative or relapse-free survival rates of the patients with ovarian cancer as an independent factor ( P  < 0.05).    Conclusions  Our findings indicate that aberrant REG4 expression plays an essential role in early ovarian carcinogenesis and is closely linked to mucinous ovarian tumors, differentiation and adverse prognosis of ovarian cancer by modulating proliferation, apoptosis, migration and invasion.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-015-1435-2) contains supplementary material, which is available to authorized users.

The role of the REG4 gene and its encoding product in ovarian epithelial carcinoma