Abstract
Homeobox B4 (HOXB4), which belongs to the homeobox (HOX) family, possesses transcription factor activity and has a crucial role in stem cell self-renewal and tumorigenesis. However, its biological function and exact mechanism in cervical cancer remain unknown. Here, we found that HOXB4 was markedly downregulated in cervical cancer. We demonstrated that HOXB4 obviously suppressed cervical cancer cell proliferation and tumorigenic potential in nude mice. Additionally, HOXB4-induced cell cycle arrest at the transition from the G0/G1 phase to the S phase. Conversely, loss of HOXB4 promoted cervical cancer cell growth both in vitro and in vivo. Bioinformatics analyses and mechanistic studies revealed that HOXB4 inhibited the activity of the Wnt/β-catenin signaling pathway by direct transcriptional repression of β-catenin. Furthermore, β-catenin re-expression rescued HOXB4-induced cervical cancer cell defects. Taken together, these findings suggested that HOXB4 directly transcriptional repressed β-catenin and subsequently inactivated the Wnt/β-catenin signaling pathway, leading to significant inhibition of cervical cancer cell growth and tumor formation.
Highlights
Cervical cancer, which is the fourth most commonly diagnosed type of cancer and the fourth leading cause of cancer-related death among females, causes an estimated 570,000 cases and 311,000 deaths in 2018 worldwide[1]
Oncomine analysis showed that Homeobox B4 (HOXB4) was upregulated in breast cancer and downregulated in colorectal cancer, indicating that HOXB4 may have a dual role in cancer pathogenesis (Fig. 1b)
These data indicated that compared with the normal cervix, the HOXB4 expression was downregulated in cervical cancer
Summary
Cervical cancer, which is the fourth most commonly diagnosed type of cancer and the fourth leading cause of cancer-related death among females, causes an estimated 570,000 cases and 311,000 deaths in 2018 worldwide[1]. It remains to be the second leading cause of cancer-related death in women aged 20–39 years after breast cancer[2]. Human papillomavirus (HPV) infection is clearly a necessary but not a sufficient cause of cervical cancer[1,3]. The WNT signal transduction cascade orchestrates embryonic development, tissue homeostasis, and regeneration[4].
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