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Abstract
Transcriptional factor HOXB9, a part of the HOX gene family, plays a crucial role in the development of diverse cancer types. This study aimed to elucidate the regulatory mechanism of HOXB9 on the proliferation and invasion of laryngeal squamous cell carcinoma (LSCC) cells to provide guidance for the development and prognosis of LSCC. The CRISPR/Cas9 method was employed in LSCC cell lines to knock out the HOXB9 gene and validate its effects on the proliferation, migration, invasion, and regulation of LSCC cells. CCK-8 and flow cytometry were used to detect cell viability and proliferation; Tunnel was used to detect cell apoptosis, and transwell was used to detect cell migration and invasion. The effect of HOXB9 on tumor growth was tested in nude mice. The downstream target genes regulated by HOXB9 were screened by microarray analysis and verified by Western blotting, immunohistochemistry, chromatin immunoprecipitation, and double-luciferase reporter assays. The current research investigated molecular pathways governed by HOXB9 in the development of LSCC. Additionally, both laboratory- and living-organism-based investigations revealed that disrupting the HOXB9 gene through the CRISPR/CAS9 mechanism restrained cellular growth, movement, and infiltration, while enhancing cellular apoptosis. Detailed analyses of LSCC cell strains and human LSCC samples revealed that HOXB9 promoted LSCC progression by directly elevating the transcriptional activity of MMP12. HOXB9 could influence changes in LSCC cell functions, and the mechanism of action might be exerted through its downstream target gene, MMP12.
Highlights
Among all head and neck cancers, laryngeal squamous cell carcinoma (LSCC)remains as the second most common malignant squamous cell carcinoma.[1]
The results revealed that the mRNA expression of HOXB9 in the laryngeal squamous cell cancer (LSCC) cell lines were higher than that in HaCaT (Figure 1A)
The protein expression of HOXB9 was detected by western blot, and it was revealed that the expression of HOXB9 in the LSCC cell lines were higher than that in the human keratinocyte HaCaT (Figure.1B)
Summary
Among all head and neck cancers, laryngeal squamous cell carcinoma (LSCC)remains as the second most common malignant squamous cell carcinoma.[1]. The HOX gene has been reported to play an important role in human embryonic development and cell differentiation.[3]. A large number of literatures have reported that the HOX gene is involved in the occurrence and development of different tumors, such as breast cancer, leukemia, lung cancer and gastric cancer.[8-13]. This plays an important role in embryonic development and cancer progression. The HOX family transcription factor HOXB9 is a crucial element in the progression of various cancers. Results: The present study explored the molecular mechanisms of HOXB9 in LSCC progression. Mechanistic studies in LSCC cell lines and human LSCC specimens demonstrated that HOXB9 promotes LSCC progression by directly upregulating the MMP12 expression at the level of its transcription. Conclusions: Collectively, the present study is the first to demonstrate the role of HOXB9 in the regulation of LSCC progression by enhancing the upregulation of MMP12.
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