Department of Gastrointestinal surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, China.
Department of Gastrointestinal surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China.
Gene. 2019 Jan 10;681:62-68. doi: 10.1016/j.gene.2018.09.051. Epub 2018 Sep 26.
Homeobox A5 (HOXA5) is a member of the HOX protein family which were implicated in serval critical process and was cancer-specific dysregulated in human cancers. However, its expression and function in human gastric cancer (GC) was still largely unknown. In this study, we confirmed for the first time that HOXA5 mRNA and protein was down-regulated in GC tissues and cell lines. Clinical data showed that low HOXA5 was significantly associated poor prognostic features, including large tumor size and advanced TNM stage. For 5-year survival, HOXA5 served as a potential prognostic marker of GC patients. Notably, HOXA5 inhibited cell viability, colony formation, proliferation, cell cycle progression and promoted apoptosis in vitro and in vivo. Furthermore, we demonstrated that HOXA5 expression was regulated by miR-196a. In GC tissues, miR-196a has an inverse correlation with HOXA5 expression. Conclusively, our results demonstrated that HOXA5 functions as a tumor suppressor in regulating tumor growth of GC under regulation of miR-196a, supporting its potential utility as a therapeutic target for GC.
Homeobox A5 (HOXA5) 是 HOX 蛋白家族的成员之一，该家族参与了多个关键过程，并在人类癌症中特异性失调。然而，其在人类胃癌 (GC) 中的表达和功能仍知之甚少。在这项研究中，我们首次证实 HOXA5 mRNA 和蛋白在 GC 组织和细胞系中下调。临床数据表明，低水平的 HOXA5 与不良预后特征显著相关，包括肿瘤体积大和 TNM 分期较晚。对于 5 年生存率，HOXA5 可作为 GC 患者的潜在预后标志物。值得注意的是，HOXA5 可抑制体外和体内的细胞活力、集落形成、增殖、细胞周期进程，并促进细胞凋亡。此外，我们证明 HOXA5 的表达受 miR-196a 调控。在 GC 组织中，miR-196a 与 HOXA5 的表达呈负相关。总之，我们的研究结果表明，HOXA5 作为一种肿瘤抑制因子，通过 miR-196a 调节 GC 的肿瘤生长，支持其作为 GC 治疗靶点的潜在应用价值。
