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.

中文翻译：

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人癌症中 SCD1 失调的综合分析和食管鳞状细胞癌中 miR-181a-5p/SCD1 轴的功能验证


食管鳞状细胞癌 （ESCC） 是最致命的癌症之一，已成为一个全球性的健康问题。硬脂酰辅酶 A 去饱和酶 1 （SCD1） 已被证明在人类癌症中起着至关重要的作用。然而，迄今为止，泛癌种分析显示的证据很少。在目前的研究中，我们系统地检查了 SCD1 在多种人类癌症中的表达模式和潜在临床结果。SCD1 在几种类型的癌症中失调，其异常表达作为诊断生物标志物，表明 SCD1 可能在肿瘤发生中发挥作用。我们以 ESCC 为例，证明 SCD1 在 ESCC 的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 SCD1 表达与 ESCC 患者不良的无进展生存期 （PFS） 和无病生存期 （DFS） 相关。通过 PINA 数据库和 Gephi 进行蛋白质-蛋白质相互作用 （PPI） 网络和模块分析，以确定枢纽靶点。同时，通过基因本体论 （GO） 和京都基因与基因组百科全书 （KEGG） 通路富集分析构建这些枢纽的功能注释分析。在功能上，ESCC 细胞中 SCD1 的功能获得促进了细胞增殖、迁移和侵袭;相比之下，ESCC 细胞中 SCD1 的功能丧失具有相反的作用。生物信息学、QPCR、Western blotting 和荧光素酶测定表明，SCD1 是 ESCC 细胞中 miR-181a-5p 的直接靶点。此外，ESCC 细胞中 miR-181a-5p 的功能获得降低了细胞生长、迁移和侵袭能力。相反，其抑制剂在 ESCC 细胞中抑制 miR-181a-5p 表达具有相反的生物学效应。 重要的是，miR-181a-5p 模拟 ESCC 转染子中增强的 SCD1 逆转了 miR-181a-5p 模拟预防的 ESCC 细胞恶性表型。综上所述，这些结果表明 SCD1 表达影响多种癌症的肿瘤进展，miR-181a-5p/SCD1 轴可能是 ESCC 治疗的潜在治疗靶点。