Li Junqiang, Yang Jing, Hua Lei, Wang Ronglin, Li Hong, Zhang Chao, Zhang Haihua, Li Shanshan, Zhu Liaoliao, Su Haichuan
Department of Oncology, Tangdu Hospital, Air Force Medical University Xi'an 710038, Shaanxi, China.
Department of Pulmonary and Critical Care Medicine, Tangdu Hospital, Air Force Medical University Xi'an 710038, Shaanxi, China.
Am J Cancer Res. 2021 Jan 1;11(1):92-107. eCollection 2021.
Epithelium-specific Ets protein 3 (Ese-3), a member of the Ets family of transcription factors, plays an important role in the development of cancers. However, little is known concerning its role in colon cancer (CC). In this study, we demonstrate that the expression of Ese-3 is upregulated in CC tissues and elevated Ese-3 expression is relationship with advanced T stage (=0.037) and poor disease-free survival (DFS, =0.044). Univariate and multivariate cox regression analyses show that Ese-3 expression may be an independent prognostic value for CC patients. Moreover, Ese-3 knockdown suppresses CC cell proliferation in vitro and in vivo, while Ese-3 overexpression has the opposite result. Further, we first demonstrate that EHD2 and INPP4B are the downstream genes of Ese-3. Subsequent investigation find that EHD2 is downregulated in CC tissues and knockdown of EHD2 significantly increase CC cell proliferation in vitro and vivo. Our findings reveal that Ese-3 promotes CC cell proliferation by downregulating EHD2 and transactivating INPP4B, and targeting the pathway may be a promising therapeutic target for CC patients.
上皮特异性Ets蛋白3（Ese-3）是Ets转录因子家族的成员之一，在癌症发展过程中发挥重要作用。然而，关于其在结肠癌（CC）中的作用却知之甚少。在本研究中，我们证明Ese-3在CC组织中的表达上调，且Ese-3表达升高与晚期T分期（P=0.037）及较差的无病生存期（DFS，P=0.044）相关。单因素和多因素cox回归分析表明，Ese-3表达可能是CC患者的一个独立预后指标。此外，敲低Ese-3可在体外和体内抑制CC细胞增殖，而Ese-3过表达则产生相反的结果。此外，我们首次证明EHD2和INPP4B是Ese-3的下游基因。随后的研究发现，EHD2在CC组织中表达下调，敲低EHD2可在体外和体内显著增加CC细胞增殖。我们的研究结果表明，Ese-3通过下调EHD2和反式激活INPP4B促进CC细胞增殖，针对该通路可能是CC患者一个有前景的治疗靶点。
