The primary regulatory gene for fatty acid synthesis, stearoyl-CoA desaturase 1 (SCD1), has been linked to the progression of several malignancies. Its role in cervical cancer remains unclear till now. This paper aimed to explore the role and mechanism of SCD1 in cervical cancer. The GEPIA database was used to perform a bioinformatics analysis of the role of SCD1 in cervical cancer staging and prognosis. The influences of SCD1 knockdown on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progress were then investigated. Following transcription factor Kruppel like factor 9 (KLF9) was discovered to be negatively correlated with SCD1, the regulatory role of KLF9 in the effects of SCD1 on cervical cancer cells and the signaling pathway was evaluated. According to the GEPIA database, SCD1 level was associated with the cervical cancer stage, the overall survival level, and the disease-free survival level. Cell proliferation, migration, invasion, and EMT progress were all hindered when its expression was knocked down. Novelty, KLF9 reversed the effects of SCD1 on cells, as well as the Akt/glycogen synthase kinase 3β (GSK3β) signaling pathway. Together, SCD1 was negatively regulated by KLF9 and it activated the Akt/GSK3β signaling pathway to promote the malignant progression of cervical cancer cells. Developing SCD1 inhibitors offers novel ideas for the biological treatment of cervical cancer.

Objective To investigate the role of fucoxanthin, reported to have significant anticancer effects, and histone Cluster 1 H3 Family Member D (HIST1H3D; implicated in tumorigenesis) in cervical cancer. Methods The half maximal inhibitory concentration (IC50) of fucoxanthin against HeLa and SiHa cervical cancer cells was determined. Differentially expressed genes (DEGs) in SiHa cells treated with IC50 fucoxanthin were screened by high-throughput techniques and subjected to signal enrichment. Following identification of HIST1H3D as a candidate gene, HIST1H3D-knockdown models were created via transfection with a short hairpin HIST1H3D payload. Impacts on cell proliferation, cell-cycle distribution, colony formation, and apoptosis were studied. Results The fucoxanthin IC50 was 1 445 and 1 641 µM (Hela and SiHa cells, respectively). Chip results revealed 2 255 DEGs, including 943 upregulated and 1 312 downregulated genes, in fucoxanthin-treated versus untreated SiHa cells. Disease and function analysis indicated that these DEGs are primarily associated with cancer and organismal injuries and abnormalities, and online integrated pathway analysis showed that the DEGs were mainly enriched in p53 signalling. HIST1H3D was significantly downregulated in response to fucoxanthin. Inhibition of HIST1H3D mRNA significantly reduced cell proliferation and colony formation, significantly augmented the percentage of apoptotic HeLa and SiHa cells, and cells were arrested in G0/G1 cell cycle phase. Conclusion The results suggest that HIST1H3D may be an oncogene in cervical carcinogenesis and a potential fucoxanthin target in treating cervical cancer.

Prostaglandin E2 (PGE2) is a potent lipid mediator of inflammation that modulates immune cell function by binding to unique G protein‐coupled receptors (EP receptors). PGE2 production increases during microbial infection and inflammation. In this study, we assessed the effect of PGE2 on the phagocytosis of bacteria by neutrophils, which are key players during infection and inflammation. We also looked for specific EP receptor signaling pathways that contributed to the neutrophil phagocytic activity. PGE2 (50–1000 ng/ml) inhibited the phagocytosis of Escherichia coli by HL‐60 human neutrophils in a concentration‐dependent manner. Inhibition of neutrophil phagocytosis by PGE2 correlated with increased intracellular cyclic adenosine monophosphate (cAMP) production, and forskolin, an adenosyl cyclase agonist, confirmed the inhibitory effect of cAMP stimulation on neutrophil phagocytosis. The expression of EP2 receptors by HL‐60 cells was confirmed by western blot analysis, and selective agonism of EP2 receptors mimicked the inhibition of phagocytosis by PGE2. The EP2 receptor antagonist AH‐6089 partially blocked the inhibition of neutrophil phagocytosis PGE2. Specific inhibition of phosphatase and tensin homolog (PTEN) enzyme attenuated the inhibition of neutrophil phagocytosis by PGE2, and both PGE2 and increased intracellular cAMP increased neutrophil PTEN activity, which was associated with decreased PTEN phosphorylation. The results support negative regulation of the antimicrobial activity of neutrophils (i.e., phagocytosis), which has important implications for the future management of bacterial infections.

Purpose To investigate the prognostic value of N6-methyladenosine (m6A)-, 5-methylcytosine (m5C)-, and N1-methyladenosine (m1A)-related genes in cervical cancer (CESC) and predicting immunotherapy response. Methods We downloaded cervical cancer mRNA expression profiles, clinical data, and m6A, m5C, m1A-related genes from public databases, and subjected them to serial bioinformatics analysis and clinical sample validation. Results Differential analysis revealed 106 methylation-related differential genes (MEDs), including 44 differentially downregulated and 62 upregulated genes. We then obtained methylation models containing 10 genes by univariate and multifactorial COX analysis. High risk genes with HR > 1 include IQGAP3, PTBP1, STAC3, CUX1, SLC2A1, and CA2, and low risk genes with HR < 1 include IGBP1, DUOX1, CHAF1A, and STAC3. We verified the accuracy of the model from inside TCGA and outside GSE39001 (AUC = 0.729). K-M analysis showed shorter survival times in the High-risk group, and Immunocytic infiltration analysis showed model genes closely associated with six immune cells. The high-risk group may benefit more effectively from immunosuppressive therapy, especially anti-CTLA-4 therapy ( p < .05). We also screened nine drugs for potential treatment and verified the expression of three key genes SLC2A1, CUX1, and CA2 using immunohistochemistry and RT-qPCR experiments with clinical samples. Conclusion We identified a prognostic model using m6A/m5C/m1A-related genes in cervical cancer, which can predict survival time and correlate with immune cell infiltration. Additionally, anti-CTLA-4 may be used as an immunotherapeutic agent for cervical cancer. KEY MESSAGES Cervical cancer still has a high mortality rate, we aim to establish a strong prognostic index and new treatment goals for improving patient survival. The role of three types of RNA methylation modifications, m6A, m5C, and m1A, in cervical cancer, remains unknown. Therefore, it is essential to explore the potential molecular mechanisms of m6A, m5C, and m1A methylation regulation in cervical cancer. We also screened nine drugs for potential treatment and anti-CTLA-4 may be used as an immunotherapeutic agent for cervical cancer. We verified the expression of three key genes SLC2A1, CUX1, and CA2