脂肪酸合酶（FASN）通过 Akt/mTOR 信号通路抑制宫颈鳞状细胞癌（CESC）的进展。
Fatty acid synthase (FASN) inhibits the cervical squamous cell carcinoma (CESC) progression through the Akt/mTOR signaling pathway.
机构信息
Vascular Breast Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, China; Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, China.
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
出版信息
Gene. 2023 Jan 30;851:147023. doi: 10.1016/j.gene.2022.147023. Epub 2022 Nov 12.
BACKGROUND
Cervical cancer is a malignant tumor that affects females and remains the cause of the highest morbidity and mortality among women worldwide. Currently, gene-targeted therapy is a novel treatment option for clinicians. Furthermore, fatty acid synthase (FASN) plays a therapeutic role in various cancers. Nonetheless, the mechanism of action of this enzyme in cervical squamous cell carcinoma and cervical duct adenocarcinoma (CESC) has not yet been reported.
METHODS
RNA (ribonucleic acid) sequencing data and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). The expression levels of FASN were obtained from Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Human Protein Atlas (HPA). Univariate and multivariate Cox regression analyses were utilized to assess independent prognostic factors associated with survival. A nomogram and receiver operating characteristic curve (ROC) were employed to evaluate survival and predictive power. In vitro experiments and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) were conducted to identify cell interference efficiency. MTS, monoclonal formation, and EDU assays were used to determine cell viability. Wound healing and invasion assays (transwell assay) were used to evaluate cell migration and invasion. Finally, Hoechst 33342, propidium iodide (PI) staining and Annexin V-FITC staining were used to assess apoptosis and the cell cycle, while western blotting was utilized to determine the protein expression levels.
RESULTS
FASN was aberrantly expressed in various cancers, including CESC, where it was highly expressed. Kaplan-Meier, univariate, multivariate Cox regression analyses and ROC curve indicated that FASN is a potential key indicator of survival prognosis among CESC patients and demonstrated good predictive ability and efficacy. Complementary in vitro experiments confirmed that FASN is an important target for CESC therapy.
CONCLUSION
The current study validated the biological and clinical significance of FASN in CESC prognosis, suggesting that FASN knockdown may exert antitumor activity against cervical cancer through the Akt/mTOR signaling pathway.
背景
宫颈癌是一种恶性肿瘤，影响女性，仍是全球女性发病率和死亡率最高的原因。目前，基因靶向治疗是临床医生的一种新的治疗选择。此外，脂肪酸合酶（FASN）在各种癌症中具有治疗作用。然而，这种酶在宫颈鳞状细胞癌和宫颈管腺癌（CESC）中的作用机制尚未报道。
方法
从癌症基因组图谱（TCGA）和基因-组织表达（GTEx）中获得 RNA（核糖核酸）测序数据和临床信息。FASN 的表达水平从基因表达谱分析交互式分析 2（GEPIA2）和人类蛋白质图谱（HPA）获得。利用单变量和多变量 Cox 回归分析评估与生存相关的独立预后因素。采用列线图和接受者操作特征曲线（ROC）评估生存和预测能力。进行体外实验和实时定量逆转录聚合酶链反应（RT-qPCR）以确定细胞干扰效率。MTS、单克隆形成和 EDU 测定用于测定细胞活力。伤口愈合和侵袭实验（transwell 实验）用于评估细胞迁移和侵袭。最后，使用 Hoechst 33342、碘化丙啶（PI）染色和 Annexin V-FITC 染色评估细胞凋亡和细胞周期，同时使用 Western blot 测定蛋白表达水平。
结果
FASN 在包括 CESC 在内的各种癌症中表达异常，在 CESC 中表达较高。Kaplan-Meier、单变量、多变量 Cox 回归分析和 ROC 曲线表明，FASN 是 CESC 患者生存预后的潜在关键指标，具有良好的预测能力和疗效。补充的体外实验证实，FASN 是 CESC 治疗的重要靶点。
结论
本研究验证了 FASN 在 CESC 预后中的生物学和临床意义，表明 FASN 敲低可能通过 Akt/mTOR 信号通路对宫颈癌发挥抗肿瘤活性。
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