Background The Jumonji-domain containing 3 has diverse roles in multiple cancers. Here, we investigated its prognostic significance in esophageal squamous cell carcinoma. Methods By using immunohistochemistry, the Jumonji-domain containing 3 expression was examined in 109 surgically resected esophageal squamous cell carcinomas and correlated with treatment outcome. The functional role of Jumonji-domain containing 3 in esophageal squamous cell carcinoma cells was determined by Jumonji-domain containing 3–mediated small interfering ribonucleic acid. Results Univariate analysis showed that Jumonji-domain containing 3 overexpression was associated with inferior overall survival (P = .004) and disease-free survival (P = .002). In a multivariate comparison, Jumonji-domain containing 3 overexpression remained independently associated with worse overall survival (P = .017, hazard ratio = 1.898) and disease-free survival (P = .011, hazard ratio = 1.901). The 5-year overall and disease-free survival rates were 66% and 58% in patients with a low expression of Jumonji-domain containing 3 and 34% and 27% in patients with overexpression of Jumonji-domain containing 3. Silencing Jumonji-domain containing 3 in esophageal squamous cell carcinoma cells inhibited cell growth rate and bromodeoxyuridine incorporation ability. In contrast, a gain of function of Jumonji-domain containing 3 promoted esophageal squamous cell carcinoma cell proliferation. Furthermore, Jumonji-domain containing 3 expression contributes to Ras/MEK pathway. Conclusion Jumonji-domain containing 3 overexpression was independently associated with poor prognosis in patients with esophageal squamous cell carcinoma. In vitro, Jumonji-domain containing 3 expression regulated esophageal squamous cell carcinoma cell growth. These results may further elucidate the role of Jumonji-domain containing 3 in esophageal squamous cell carcinoma and provide a potential new therapeutic approach for patients with esophageal squamous cell carcinoma.
