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HOXB9 通过上调 MMP12 促进喉鳞状细胞癌的进展。

HOXB9 promotes laryngeal squamous cell carcinoma progression by upregulating MMP12.

机构信息

Department of Otorhinolaryngology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, 550001, Guiyang, Guizhou, People's Republic of China.

Department of Otorhinolaryngology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xue Fu Road, 150001, Harbin, Heilongjiang, People's Republic of China.

出版信息

Funct Integr Genomics. 2024 Apr 18;24(3):78. doi: 10.1007/s10142-024-01357-4.

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.

摘要

转录因子 HOXB9 是 HOX 基因家族的一部分,在多种癌症类型的发展中起着关键作用。本研究旨在阐明 HOXB9 对喉鳞状细胞癌 (LSCC) 细胞增殖和侵袭的调控机制,为 LSCC 的发生发展和预后提供指导。本研究采用 CRISPR/Cas9 方法敲除 LSCC 细胞系中的 HOXB9 基因,并验证其对 LSCC 细胞增殖、迁移、侵袭和调控的影响。CCK-8 和流式细胞术检测细胞活力和增殖;Tunnel 检测细胞凋亡,Transwell 检测细胞迁移和侵袭。采用裸鼠检测 HOXB9 对肿瘤生长的影响。通过微阵列分析筛选 HOXB9 调控的下游靶基因,并通过 Western blot、免疫组化、染色质免疫沉淀和双荧光素酶报告基因检测进行验证。本研究探讨了 HOXB9 在 LSCC 发生发展中的分子通路。此外,实验室和活体研究均表明,通过 CRISPR/CAS9 机制破坏 HOXB9 基因可抑制细胞生长、迁移和浸润,同时增强细胞凋亡。对 LSCC 细胞株和人 LSCC 样本的详细分析表明,HOXB9 通过直接提高 MMP12 的转录活性促进 LSCC 进展。HOXB9 可影响 LSCC 细胞功能的变化,其作用机制可能通过下游靶基因 MMP12 发挥作用。

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