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通过全面转录组分析鉴定与喉鳞状细胞癌 Fascin 肌动蛋白结合蛋白 1 相关的新型分子和通路。

Identification of novel molecules and pathways associated with fascin actin‑bundling protein 1 in laryngeal squamous cell carcinoma through comprehensive transcriptome analysis.

机构信息

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

Department of Anatomy, the Basic Medical School of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

出版信息

Int J Mol Med. 2024 Apr;53(4). doi: 10.3892/ijmm.2024.5363. Epub 2024 Mar 1.

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor with a poor prognosis. Fascin actin‑bundling protein 1 (FSCN1) has been reported to play a crucial role in the development and progression of LSCC; however, the underlying molecular mechanisms remain unknown. Herein, a whole transcriptome microarray analysis was performed to screen for differentially expressed genes (DEGs) in cells in which FSCN1 was knocked down. A total of 462 up and 601 downregulated mRNA transcripts were identified. Functional annotation analysis revealed that these DEGs were involved in multiple biological functions, such as transcriptional regulation, response to radiation, focal adhesion, extracellular matrix‑receptor interaction, steroid biosynthesis and others. Through co‑expression and protein‑protein interaction analysis, FSCN1 was linked to novel functions, including defense response to virus and steroid biosynthesis. Furthermore, crosstalk analysis with FSCN1‑interacting proteins revealed seven DEGs, identified as FSCN1‑interacting partners, in LSCC cells, three of which were selected for further validation. Co‑immunoprecipitation validation confirmed that FSCN1 interacted with prostaglandin reductase 1 and 24‑dehydrocholesterol reductase (DHCR24). Of note, DHCR24 is a key enzyme involved in cholesterol biosynthesis, and its overexpression promotes the proliferation and migration of LSCC cells. These findings suggest that DHCR24 is a novel molecule associated with FSCN1 in LSCC, and that the FSCN1‑DHCR24 interaction may promote LSCC progression by regulating cholesterol metabolism‑related signaling pathways.

摘要

喉鳞状细胞癌(LSCC)是一种预后不良的常见恶性肿瘤。有报道称,细丝蛋白 actin 束状蛋白 1(FSCN1)在 LSCC 的发生和发展中起着至关重要的作用;然而,其潜在的分子机制尚不清楚。在此,进行了全转录组微阵列分析,以筛选 FSCN1 敲低的细胞中的差异表达基因(DEGs)。共鉴定出 462 个上调和 601 个下调的 mRNA 转录本。功能注释分析显示,这些 DEGs 参与了多种生物学功能,如转录调控、辐射反应、焦点黏附、细胞外基质-受体相互作用、甾体生物合成等。通过共表达和蛋白质-蛋白质相互作用分析,FSCN1 与新的功能相关联,包括对病毒的防御反应和甾体生物合成。此外,与 FSCN1 相互作用蛋白的串扰分析显示,在 LSCC 细胞中鉴定出 7 个 DEGs 为 FSCN1 相互作用伙伴,其中 3 个被选择进一步验证。共免疫沉淀验证证实 FSCN1 与前列腺素还原酶 1 和 24-去氢胆固醇还原酶(DHCR24)相互作用。值得注意的是,DHCR24 是胆固醇生物合成中的关键酶,其过表达促进 LSCC 细胞的增殖和迁移。这些发现表明,DHCR24 是与 LSCC 中 FSCN1 相关的新型分子,FSCN1-DHCR24 相互作用可能通过调节胆固醇代谢相关信号通路促进 LSCC 进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5080/10914310/7978ac9253ad/ijmm-53-04-05363-g00.jpg

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