HOXB9 promotes laryngeal squamous cell carcinoma progression by upregulating MMP12

细胞生长 生物 癌症研究 流式细胞术 细胞 染色质免疫沉淀 微阵列分析技术 基因 细胞迁移 细胞凋亡 细胞生物学 分子生物学 基因表达 遗传学 发起人
作者
Chuanhui Sun,Hua Deng,Qiuying Li,Peng Wang,Yujiang Chen,Yanan Sun,Changsong Han
出处
期刊:Functional & Integrative Genomics [Springer Science+Business Media]
卷期号:24 (3) 被引量:1
标识
DOI:10.1007/s10142-024-01357-4
摘要

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.
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