Fatty acid synthase (FASN) inhibits the cervical squamous cell carcinoma (CESC) progression through the Akt/mTOR signaling pathway

Abstract

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.

Keywords: Akt; CESC; FASN; Progression; mTOR.