Journal
AGING-US
Volume 13, Issue 5, Pages 6606-6624Publisher
IMPACT JOURNALS LLC
Keywords
HOXA6; PBX2; proliferation; metastasis; gastric cancer
Categories
Funding
- National Natural Science Funds of China [81772964, 81974448, 82073066]
- Guangdong gastrointestinal disease research center [2017B020209003]
- Special Scientific Research Fund of Public Welfare Profession of National Health and Family Planning Commission [201502026]
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University
- Guangdong Medical Research Foundation [B2019126]
- Shenzhen Science and Technology Innovation Commission [JCYJ20180306170328854]
- Special Foundation for Economic and Technological Development of Longgang District, Shenzhen [LGKCYLWS2018000160]
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HOXA6 gene acts as an oncogene in various cancers, and its upregulation in gastric cancer is associated with poor clinical outcomes. HOXA6 promotes cell proliferation, migration, and invasion in GC through interaction with PBX2, suggesting it may serve as a biomarker for disease progression in GC.
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.
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