Abstract
HOXA5 is considered a regulator involved in embryonic development and cellular differentiation and a tumor suppressor. Nevertheless, its biological role in cervical carcinoma is still unclear. In the present study, immunohistochemistry showed that HOXA5 expression gradually decreased as the degree of cervical lesions deepened. Ectopic expression of HOXA5 restrained cell proliferation, decreased cell viability, and inhibited tumor formation in vitro and in vivo. Furthermore, the expression of HOXA5 could arrest cell cycle from G0/G1 to S phase. RNA-seq revealed that p21 and cyclinD1 were involved in this process. Moreover, the gene set enrichment analysis and the TOP/FOP reporter assay both suggested that HOXA5 could restrain the activity of the Wnt/β-catenin pathway. Further study using dual-luciferase reporter assay and quantitative chromatin immunoprecipitation assay demonstrated that HOXA5 could directly bind to the TAAT motif within the promoter of TP53 by its HD domain and transactivate TP53, which can upregulate p21. Altogether, our data suggest that HOXA5 inhibits the proliferation and neoplasia via repression activity of the Wnt/β-catenin pathway and transactivating TP53 in cervical cancer.
Highlights
Cervical carcinoma ranked 4th in both morbidity and mortality in all cancer types in females globally[1]
HOXA5 is frequently downregulated in cervical cancers To understand the expression pattern of HOXA5 in cervical cancer, HOXA5 protein expression was detected in normal cervix (NC) (n = 42), high-grade squamous intraepithelial lesion (HSIL), (n = 28), and CC (n = 55) by IHC
There were several studies concerning the function of HOXA5 protein in cervical carcinoma
Summary
Cervical carcinoma ranked 4th in both morbidity and mortality in all cancer types in females globally[1]. The main cause of cervical cancer is considered to be human papillomavirus (HPV) infection[2,3], but not every patient with infection of HPV develop cervical cancers, only a small proportion of people develop cervical cancer. This phenomenon indicates that there are other elements participating in cervical carcinogenesis[4]. Recent studies indicated stem cell-related genes are related with the development of cervical cancer[5,6]. Previous studies in our laboratory demonstrated that dysfunction of stem cell-related genes, such as SOX177, SLUG8, KLF49, GDF1510, DAX111, and EZH212 may participate in cervical carcinogenesis. There is a compelling need to explore the underlying mechanism of stem cellrelated genes in cervical cancer
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