Background: It has been reported that atractylodin has a potential antitumor effect. This study aimed to investigate the effects of atractylodin on Huh7 and Hccm hepatocellular carcinoma (HCC) cells and its molecular mechanism.Methods: Huh7 and Hccm cells were cultured in vitro, and their viability was detected by CCK-8 assay and the half inhibitory concentration (IC50) was calculated. The cells were treated with different concentrations of atractylodin, and the migration and invasion ability of cells was detected by scratch assay and Transwell assay. The cell cycle change and apoptosis rate were detected by flow cytometry. IlluminaHiSeq4000 platform was used for transcriptome sequencing, and the results were analyzed for gene differential expression, gene function, and signal pathway enrichment. Morphological changes of cells were detected by transmission electron microscopy, reactive oxygen species (ROS) levels were detected by DCFH-DA probe, and the expressions of ferroptosis related proteins GPX4, ACSL4, FTL, and TFR1 were detected by Western blot. Results:The results showed that atractylodin could inhibit the proliferation, migration, and invasion of Huh7 and Hccm cells, regulate the cell cycle, and induce cell apoptosis and G1 phase cell cycle arrest. In addition, it could significantly induce the increase of intracellular ROS levels, decrease the expression of GPX4 and FTL proteins, and up-regulate the expression of ACSL4 and TFR1 proteins.Conclusions: Atractylodin can inhibit the proliferation, migration, and invasion of Huh7 and Hccm liver cancer cells, and induce cell apoptosis and cell cycle arrest. In addition, our results suggest that atractylodin may induce ferroptosis in HCC cells by inhibiting the expression of GPX4 and FTL proteins, and upregulating the expression of ACSL4 and TFR1 proteins.
Background: Lymphocyte-specific protein tyrosine kinase (LCK), an encoded Src family protein tyrosine kinase, performs a pivotal molecular signaling role in the selection and maturation processes during T-cell development. Although aberrant LCK expression is known to have a significant association with carcinogenesis, the underlying role of LCK in breast cancer (BC) is still obscure.Methods: An analysis of the levels of LCK mRNA expression in BC was performed, and the value of LCK expression for predicting the prognosis of patients with BC was studied using various online data resources, which included Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN. The web-based NetworkAnalyst tool was utilized to investigate the functional network of differentially expressed LCK. LinkedOmics was employed to identify the genes with which LCK has correlations in BC, together with the kinases, microRNAs, and transcription factors (TFs) potentially targeted by LCK in BC. The expression levels of LCK and its significantly correlated genes in BC were investigated with the Human Protein Atlas (HPA). Results:We observed a significant difference in the level of LCK mRNA expression between BC patients and healthy individuals, and a higher LCK expression was associated with poor overall survival (OS). The functional enrichment results revealed that the differential expression of LCK was mainly involved in the regulation of immune response and inflammatory response in BC. The expression of significantly related genes, such as inducible T-cell kinase (ITK), CD5, CD96, CD247, SH2 domain containing 1A (SH2D1A), phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CD), Src-like-adaptor 2 (SLA2), and interleukin 2 receptor (IL2RG), was associated with poor OS in patients with BC. Regulatory network analysis found that LCK regulated immune cells, cancer progression, apoptosis, and cell cycle signal transduction through cancerrelated kinases (ITK and MAPK3), miRNAs (miR-345 and miR-524), and TFs (AP1, SRF, and E2F1).Conclusions: This study presents new perspectives on the differential expression and prognostic value of LCK in BC. Our observations will provide a basis for further study on the oncogenic and regulatory roles of LCK in BC.
Introduction Amplification of the 11q13.3 locus has been observed in various tumors. This study sought to determine the correlation of gene amplification at the 11q13.3 locus with the immune status and survival of breast cancer. Methods Amplification of the 11q13.3 locus was characterized by analyzing a publicly available database from the cBioPortal platform (TCGA). The correlation of amplified genes with immune cell infiltration in breast cancer was further analyzed using the TIMER2.0 platform. Immunohistochemical staining was used to determine the expression levels of Cyclin D1 (CCND1), Fas-associated death domain (FADD) and P53 in 156 clinical breast cancer samples. Results This study revealed that amplification of the 11q13.3 amplicon in breast cancer is likely more frequently detected in luminal B breast cancer. Moreover, high expression or amplification of CCND1 , fibroblast growth factor 3 ( FGF3 ), fibroblast growth factor 4 ( FGF4 ), fibroblast growth factor 19 ( FGF19 ) and FADD was inversely correlated with the abundance of CD4+ T cells and dendritic cell infiltration in breast cancer ( P < 0.05). Data analysis also demonstrated that high expression of CCND1, FGF4 and FADD mRNA levels was closely correlated with shorter recurrence-free survival (RFS) in patients with breast cancer ( P < 0.05). The results of immunohistochemical staining from clinical samples further confirmed that high expression of CCND1 and FADD was frequently detected in luminal B and high-grade breast cancer with shorter metastasis-free survival times ( P < 0.05). Conclusion This study demonstrated that coamplification of genes located on the 11q13.3 amplicon is frequently detected in luminal B subtype breast cancer and is closely associated with worse survival in patients with breast cancer. Moreover, coamplification of the CCND1-FGF locus might decrease antitumor immune activity in breast cancer, indicating that coamplification of the 11q13.3 amplicon is likely to be a key determinant of therapeutic resistance and accelerate the aggressive evolution of breast cancer.
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