Coexpression of HOXA6 and PBX2 promotes metastasis in gastric cancer

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...

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Published in:Aging (Albany, NY.) NY.), 2021-03, Vol.13 (5), p.6606-6624
Main Authors: Lin, Jianjiao, Zhu, Huiqiong, Hong, Linjie, Tang, Weimei, Wang, Jing, Hu, Hongsong, Wu, Xiaosheng, Chen, Yaying, Liu, Guangnan, Yang, Qiong, Li, Jiaying, Wang, Yusi, Lin, Zhizhao, Xiao, Yizhi, Dai, Weiyu, Huang, Miaojvan, Li, Guoxin, Li, Aimin, Wang, Jide, Xiang, Li, Liu, Side
Format: Article
Language:English
Subjects:
Animals
Cell Movement
Cell Proliferation
Female
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Lung Neoplasms - secondary
Male
Mice
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Research Paper
RNA, Messenger - metabolism
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
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Summary: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.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.202426