ABSTRACT
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. The presently available understanding of the pathogenesis of ACC is incomplete and the treatment options for patients with ACC are limited. Gene marker identification is required for accurate and timely diagnosis of the disease. In order to identify novel candidate genes associated with the occurrence and progression of ACC, the microarray datasets, GSE12368 and GSE19750, were obtained from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction network (PPI) was constructed to identify significantly altered modules, and module analysis was performed using Search Tool for the Retrieval of Interacting Genes and Cytoscape. A total of 228 DEGs were screened, consisting of 29 up and 199 downregulated genes. The enriched functions and pathways of the DEGs primarily included 'cell division', 'regulation of transcription involved in G1/S transition of mitotic cell cycle', 'G1/S transition of mitotic cell cycle', 'p53 signaling pathway' and 'oocyte meiosis'. A total of 14 hub genes were identified, and biological process analysis revealed that these genes were significantly enriched in cell division and mitotic cell cycle. Furthermore, survival analysis revealed that AURKA, TYMS, GINS1, RACGAP1, RRM2, EZH2, ZWINT, CDK1, CCNB1, NCAPG and TPX2 may be involved in the tumorigenesis, progression or prognosis of ACC. In conclusion, the 14 hub genes identified in the present study may aid researchers in elucidating the molecular mechanisms associated with the tumorigenesis and progression of ACC, and may be powerful and promising candidate biomarkers for the diagnosis and treatment of ACC.
ABSTRACT
OBJECTIVE: Thapsigargin (TG) is a natural product that exists in most parts of the plant Thapsia garganica L. and possesses potential anticancer activities against variety tumor cell lines. TG induces endoplasmic reticulum (ER) stress and apoptosis by inhibiting cancer growth. However, the antineoplastic effect of TG in human adrenocortical carcinoma (ACC) cells is still unknown. METHODS: In this study, two human ACC cell lines including SW-13 and NCI-H295R were employed to explore the potential role of TG in ACC. A mouse xenograft model of SW-13 cells was established to verify the role of TG in vivo. The cell viability was tested using Cell Counting Kit-8 and Transwell assays. Flow cytometry and Hoechst 33,258 staining were employed to analyze cell apoptosis. RT-qPCR and Western blot (WB) were performed to explore the underlying mechanism of TG-induced apoptosis in ACC cells. RESULTS: The results indicated that TG dose-dependently inhibited proliferation, migration and invasion in human ACC cells. TG significantly increased the mitochondrial rate of apoptosis and ER stress activity in ACC cells and suppressed ACC xenograft growth in vivo. In addition, the expression of Jun N-terminal kinase (JNK) signaling-related genes and proteins was upregulated by the treatment with TG. CONCLUSION: Our findings suggest that TG inhibits the viability of ACC cells by inducing apoptosis through the activation of JNK signaling. Thus, TG is expected to be a potential candidate for the treatment of ACC.
