Abstract
BackgroundHOXA1 is a member of the Homeobox gene family, which encodes a group of highly conserved transcription factors that are important in embryonic development. However, it has been reported that HOXA1 exhibits oncogenic properties in many malignancies. This study focused on the expression and clinical significance of HOXA1 in gastric cancer (GC).MethodsTo assess the mRNA and protein expression of HOXA1 and cyclin D1 in GC tissues, we utilized qRT-PCR and western blotting, respectively. The effects of HOXA1 on GC cell proliferation, migration, and invasion, as well as xenograft tumor formation and the cell cycle were investigated in our established stable HOXA1 knockdown GC cell lines. The protein expression of HOXA1 and cyclin D1 was examined by immunohistochemistry using GC tissue microarrays (TMA) to analyze their relationship on a histological level. The Kaplan-Meier method and cox proportional hazards model were used to analyze the relationship of HOXA1 and cyclin D1 expression with GC clinical outcomes.ResultsHOXA1 mRNA and protein expression were upregulated in GC tissues. Knockdown of HOXA1 in GC cells not only inhibited cell proliferation, migration, and invasion in vitro but also suppressed xenograft tumor formation in vivo. Moreover, HOXA1 knockdown induced changes in the cell cycle, and HOXA1 knockdown cells were arrested at the G1 phase, the number of cells in S phase was reduced, and the expression of cyclin D1 was decreased. In GC tissues, high cyclin D1 mRNA and protein expression were detected, and a significant correlation was found between the expression of HOXA1 and cyclin D1. Survival analysis indicated that HOXA1 and cyclin D1 expression were significantly associated with disease-free survival (DFS) and overall survival (OS). Interestingly, patients with tumors that were positive for HOXA1 and cyclin D1 expression showed worse prognosis. Multivariate analysis confirmed that the combination of HOXA1 and cyclin D1 was an independent prognostic indicator for OS and DFS.ConclusionOur data show that HOXA1 plays a crucial role in GC development and clinical prognosis. HOXA1, alone or combination with cyclin D1, may serve as a novel prognostic biomarker for GC.
Highlights
HOXA1 is a member of the Homeobox gene family, which encodes a group of highly conserved transcription factors that are important in embryonic development
HOXA1 is upregulated in gastric cancer (GC) tissues compared to the levels in corresponding adjacent normal mucosae The mRNA expression of HOXA1 was examined in 48 GC tissue and paired mucosa samples by quantitative real-time PCR (qRT-PCR)
Knockdown of HOXA1 expression inhibits GC cell proliferation To explore the function of HOXA1 in GC, we suppressed the expression of HOXA1
Summary
HOXA1 is a member of the Homeobox gene family, which encodes a group of highly conserved transcription factors that are important in embryonic development. This study focused on the expression and clinical significance of HOXA1 in gastric cancer (GC). HOX genes, which were first discovered in Drosophila melanogaster mutants in the early 1900s, constitute a highly conserved subgroup of the homeobox superfamily that encodes transcription factors with a 60-amino acid domain called the homeodomain. HOX genes play important roles in embryonic development by regulating numerous processes, including cell proliferation, apoptosis, differentiation, angiogenesis, and so on [7,8,9]. HOX genes play an important role in the mechanisms underlying the following three basic precepts: spatial collinearity, posterior prevalence, and temporal collinearity [8]. Aberrant expression of HOX genes occurs in many cancers, such as acute leukemia, lung cancer, and cervical carcinoma, among others [10,11,12,13,14]
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