Research Paper|Volume 13, Issue 5|pp 6606—6624

Coexpression of HOXA6 and PBX2 promotes metastasis in gastric cancer

Jianjiao Lin^1,², Huiqiong Zhu¹, Linjie Hong¹, Weimei Tang¹, Jing Wang¹, Hongsong Hu², Xiaosheng Wu¹, Yaying Chen^1,⁴, Guangnan Liu¹, Qiong Yang^1,³, Jiaying Li¹, Yusi Wang¹, Zhizhao Lin¹, Yizhi Xiao¹, Weiyu Dai¹, Miaojvan Huang², Guoxin Li⁵, Aimin Li¹, Jide Wang^1,², Li Xiang², Side Liu^1,²

¹Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
²Department of Gastroenterology, Longgang District People’s Hospital, Shenzhen 518172, China
³The Second Affiliated Hospital of University of South China, Hengyang 421001, China
⁴Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510515, China
⁵Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Received: March 6, 2020Accepted: November 3, 2020Published: February 1, 2021

https://doi.org/10.18632/aging.202426

Copyright: © 2021 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 in vitro. In vivo, 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.