High Expression Of HOXA1 And Its Molecular Mechanism In Gastric Cancer

Objectives: HOX gene family is one member of the homeobox gene.It not only encodes transcription factors that regulate cell proliferation and differentiation,but also has a relation with the occurrence,development and prognosis of a variety of human malignancies.HOXA1 is a member of the HOX gene family.Our group has reported that the expression of HOXA1 was up-regulated in gastric cancer(GC)tissues.Therefore,on the basis of our preliminary research,the purpose of this study is to focus on the expression of HOXA1 and its possible mechanism in GC.Methods: Firstly,Real-time PCR and Western blot were utilized to assess the m RNA and protein expression of HOXA1 in GC tissues.Then,the effects of HOXA1 on GC cell malignant biological behavior were investigated in our established stable HOXA1 knockdown GC cell lines.Furthermore,Real-time PCR and Western blot were utilized to assess the m RNA and protein expression of cyclin D1 in GC tissues.The protein expression of HOXA1 and cyclin D1 was examined by immunohistochemistry using GC tissue microarrays(TMA)to analyze their relationship on histological level.Then,the cox proportional hazards model and Kaplan-Meier method were used to analyze the relationship of HOXA1 and cyclin D1 expression with GC clinical outcomes combined with clinical and pathological data.Results:1?Real-time PCR and Western blot analysis revealed that HOXA1 m RNA and protein expression were elevated in GC tissues than paired adjacent normal mucosae.2 ? SGC-7901 and BGC-823 GC cells were selected to successfully constructed HOXA1 knockdown stably transfected GC cell lines.What is more,knockdown of HOXA1 in GC cells not only inhibited cell proliferation by CCK-8 assay,colony formation ability by plate colony formation assay,migration and invasion by transwell migration and invasion assays in vitro but also suppressed xenograft tumor formation by nude mice xenograft models in vivo.Moreover,HOXA1 knockdown induced changes in the cell cycle,and HOXA1 knockdown cells were arrested at the G1 phase.Meanwhile,Ed U incorporation assay showed that the DNA replication activity was reduced and the number of cells in S phase was decreased in HOXA1 knockdown cells.And we also found the expression of cyclin D1 was decreased by Western blot in our established stable GC cells,which means HOXA1 may play a role in cell cycle through cyclin D1 and promote tumor progression.3?Real-time PCR and Western blot analysis revealed that high cyclin D1 m RNA and protein expression were detected in GC tissues.And we found that the expression of HOXA1 and cyclin D1 was positively correlated.Then,the cox proportional hazards model showed that HOXA1 was an independent prognostic indicator for OS and DFS.Meanwhile,the Kaplan-Meier method indicated that HOXA1-positive and cyclin D1-positive patients had a worse prognosis.Besides,HOXA1-and cyclin D1-positive patients exhibited a much lower OS and DFS than HOXA1-or cyclin D1-positive patients or HOXA1-and cyclin D1-negative patients.Conclusions: Our results suggested that the expression of HOXA1 was up-regulated in GC tissues and HOXA1 could enhance the malignant biological behavior of GC.Meanwhile,HOXA1 may be a new prognostic marker for GC and HOXA1 combined with cyclin D1 may exhibit more significance in GC prognosis.