Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Department of Gastroenterology, Longgang District People's Hospital, Shenzhen 518172, China.
Aging (Albany NY). 2021 Feb 1;13(5):6606-6624. doi: 10.18632/aging.202426.
HOXA6 gene plays a role of the oncogene in various cancers. Nonetheless, its effect on gastric cancer (GC) occurrence and development is still unclear. We analysed whether HOXA6 interacts with the PBX2 protein using the STRING database. The molecular mechanism by which HOXA6 synergizes with PBX2 in GC metastasis is not fully understood. Here, we found that the expression of HOXA6 was increased in GC tissues and cell lines. The upregulation of HOXA6 was closely associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients based on tissue microarray (TMA) data. Moreover, the overexpression of HOXA6 promoted, whereas siRNA-mediated repression of HOXA6 inhibited, the cell proliferation, migration, and invasion of GC cells. Furthermore, HOXA6 could physically interact with and stabilize PBX2. In addition, HOXA6 and PBX2 expression was positively correlated in GC cells and tissue. HOXA6 and PBX2 suppression in GC cells also led to decreased migration and invasion potential . , HOXA6 was shown to cooperate with PBX2 to enhance cell metastasis via orthotopic implantation. These data indicate that HOXA6 promotes cell proliferation, migration, and invasion and that the HOXA6-PBX2 axis may be a useful biomarker for disease progression in GC.
HOXA6 基因在多种癌症中扮演癌基因的角色。然而，其在胃癌（GC）发生和发展中的作用尚不清楚。我们使用 STRING 数据库分析了 HOXA6 是否与 PBX2 蛋白相互作用。HOXA6 与 PBX2 在 GC 转移中协同作用的分子机制尚不完全清楚。在这里，我们发现 HOXA6 在 GC 组织和细胞系中的表达增加。基于组织微阵列（TMA）数据，HOXA6 的上调与 GC 患者的分化、淋巴结转移、AJCC 分期、TNM 分期和不良生存结局密切相关。此外，HOXA6 的过表达促进了 GC 细胞的增殖、迁移和侵袭，而 siRNA 介导的 HOXA6 抑制则抑制了 GC 细胞的增殖、迁移和侵袭。此外，HOXA6 可以与 PBX2 物理相互作用并稳定 PBX2。此外，HOXA6 和 PBX2 在 GC 细胞和组织中的表达呈正相关。GC 细胞中 HOXA6 和 PBX2 的抑制也导致迁移和侵袭潜力降低。HOXA6 还与 PBX2 合作通过原位植入增强细胞转移。这些数据表明，HOXA6 促进细胞增殖、迁移和侵袭，HOXA6-PBX2 轴可能是 GC 疾病进展的有用生物标志物。
