PDF(Pubmed)
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）是一种常见的恶性肿瘤，预后较差。据报道，Fascin肌动蛋白束蛋白1（FSCN1）在LSCC的发生和发展中起着至关重要的作用；然而，潜在的分子机制仍然未知。在这里，我们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).鉴定了总共462个上调的mRNA转录物和601个下调的mRNA转录物。功能注释分析表明，这些DEGs参与多种生物学功能，如转录调控，对辐射的反应,病灶粘连,细胞外基质-受体相互作用，类固醇生物合成和其他。通过共表达和蛋白质-蛋白质相互作用分析，FSCN1与新功能有关，包括对病毒和类固醇生物合成的防御反应。此外，与FSCN1相互作用蛋白的串扰分析揭示了七个DEG，被确定为FSCN1相互作用伙伴，在LSCC细胞中，选择其中3例进行进一步验证.免疫共沉淀验证证实FSCN1与前列腺素还原酶1和24-脱氢胆固醇还原酶（DHCR24）相互作用。值得注意的是，DHCR24是参与胆固醇生物合成的关键酶,其过度表达促进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。
