Abstract
HOXB9, as a HOX family transcription factor, playing a significant role in embryonic development and cancer progression. However, the function of HOXB9 and its precise mechanism in regulating endometrial cancer progression remains unknown. Here, we demonstrated that the expression of HOXB9 was increased in endometrial cancer, and associated with histological grade and lymph node metastasis. In addition, elevated HOXB9 predicts a poor prognosis in endometrial cancer patients. Interestingly, bioinformatics analysis of TCGA cancer database showed that HOXB9 expression is positively correlated with E2F3 expression. Moreover, HOXB9 promoted E2F3 expression by directly targeting to its promoter. Furthermore, we found that knocking down E2F3 abolished the ability of HOXB9 in enhancing cell migration. Taken together, for the first, we demonstrated the function and mechanism of HOXB9 in regulating endometrial cancer progression, and indicated HOXB9 may be a novel prognostic marker of endometrial cancer.
Highlights
Endometrial cancer (EC) is one of the leading causes of gynecologic malignancies[1,2]
The expression of HOXB9 and its clinical significance in EC To determine the expression of HOXB9 in EC, we analyzed its expression in a series of 88 endometrial carcinoma, 15 normal proliferative endometrium and 21 atypical endometrial hyperplasia by immunohistochemistry
We found that the high expression ratio and expression level of HOXB9 in normal proliferative endometrium, atypical endometrial hyperplasia and endometrial carcinoma were gradually increased (P = 0.0196; Fig. 1b and S1a)
Summary
Endometrial cancer (EC) is one of the leading causes of gynecologic malignancies[1,2]. Surgery is the major treatment for EC, while it is quite important to develop new therapeutic strategies for EC5. The investigation of new molecular mechanisms in EC may be useful to identify new diagnostic and therapeutic targets. The HOX genes, encode a group of transcription factors, share a highly conserved homeobox domain. The whole 39 HOX genes are identified and grouped into four clusters (HOXA, B, C and D)[6,7,8]. Sequential HOX expression from 3ʹ to 5ʹ along the anteriorposterior (AP) axis could control body segmentation according to the rules of spatial and temporal collinearity[8,9,10,11]. HOXB9 together with other HOX genes controls the specification of thoracic skeletal elements and mammary gland development[12,13]
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