研究动态
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人类癌症中SCD1的失调综合分析及食管鳞癌中miR-181a-5p/SCD1轴的功能验证。

An integrated analysis of dysregulated SCD1 in human cancers and functional verification of miR-181a-5p/SCD1 axis in esophageal squamous cell carcinoma.

发表日期:2023
作者: Bing-Yen Wang, Yuan-Yen Chang, Li-Yen Shiu, Yi-Ju Lee, Yu-Wei Lin, Yu-Shen Hsu, Hsin-Ting Tsai, Sung-Po Hsu, Li-Jen Su, Meng-Hsiu Tsai, Jing-Hong Xiao, Jer-An Lin, Chang-Han Chen
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

食管鳞状细胞癌(ESCC)是最致命的癌症之一,已成为全球性健康问题。已有研究表明,硬脂酰辅酶A脱饱和酶1(SCD1)在人类癌症中起到关键作用。然而,泛癌症分析目前仅有少量证据。本研究系统检查了SCD1在多种人类癌症中的表达模式和潜在临床结果。SCD1在多种癌症中发生失调,并作为一种诊断生物标志物,表明SCD1可能在肿瘤发生中起到作用。以ESCC为例,我们证明了SCD1在ESCC肿瘤组织中显著上调,并与ESCC患者的临床病理特征相关。此外,Kaplan-Meier分析显示,高表达的SCD1与ESCC患者的无进展生存期(PFS)和无疾病生存期(DFS)呈相关性。通过PINA数据库和Gephi软件进行了蛋白质相互作用(PPI)网络和模块分析,以确定核心靶点。同时,通过基因本体论(GO)和Kyoto基因与基因组百科全书(KEGG)通路富集分析构建了这些核心靶点的功能注释分析。从功能上讲,SCD1在ESCC细胞中的过表达促进了细胞增殖、迁移和侵袭;相反,SCD1在ESCC细胞中的缺失功能则产生了相反的效果。生物信息学、QPCR、Western blot和荧光素酶分析表明,在ESCC细胞中,SCD1是miR-181a-5p的直接靶点。此外,在ESCC细胞中过表达miR-181a-5p减少了细胞生长、迁移和侵袭能力。相反,miR-181a-5p的抑制剂抑制了其在ESCC细胞中的表达,产生了相反的生物学效应。重要的是,在miR-181a-5p模拟转染ESCC细胞中加强SCD1可以逆转miR-181a-5p模拟预防ESCC细胞恶性表型的效果。综上所述,这些结果表明SCD1表达影响多种癌症的肿瘤进展,并且miR-181a-5p/SCD1轴可能是ESCC治疗的潜在治疗靶点。 © 2023年作者。
Esophageal squamous cell carcinoma (ESCC), one of the most lethal cancers, has become a global health issue. Stearoyl-coA desaturase 1 (SCD1) has been demonstrated to play a crucial role in human cancers. However, pan-cancer analysis has revealed little evidence to date. In the current study, we systematically inspected the expression patterns and potential clinical outcomes of SCD1 in multiple human cancers. SCD1 was dysregulated in several types of cancers, and its aberrant expression acted as a diagnostic biomarker, indicating that SCD1 may play a role in tumorigenesis. We used ESCC as an example to demonstrate that SCD1 was dramatically upregulated in tumor tissues of ESCC and was associated with clinicopathological characteristics in ESCC patients. Furthermore, Kaplan-Meier analysis showed that high SCD1 expression was correlated with poor progression-free survival (PFS) and disease-free survival (DFS) in ESCC patients. The protein-protein interaction (PPI) network and module analysis by PINA database and Gephi were performed to identify the hub targets. Meanwhile, the functional annotation analysis of these hubs was constructed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Functionally, the gain-of-function of SCD1 in ESCC cells promoted cell proliferation, migration, and invasion; in contrast, loss-of-function of SCD1 in ESCC cells had opposite effects. Bioinformatic, QPCR, Western blotting and luciferase assays indicated that SCD1 was a direct target of miR-181a-5p in ESCC cells. In addition, gain-of-function of miR-181a-5p in ESCC cells reduced the cell growth, migratory, and invasive abilities. Conversely, inhibition of miR-181a-5p expression by its inhibitor in ESCC cells had opposite biological effects. Importantly, reinforced SCD1 in miR-181a-5p mimic ESCC transfectants reversed miR-181a-5p mimic-prevented malignant phenotypes of ESCC cells. Taken together, these results indicate that SCD1 expression influences tumor progression in a variety of cancers, and the miR-181a-5p/SCD1 axis may be a potential therapeutic target for ESCC treatment.© 2023 The Authors.