This study was specifically designed to confirm the hypothesis that microRNA-200c (miR-200c) affects the development of cisplatin (DDP) resistance in human gastric cancer cells by targeting zinc finger E-box binding homeobox 2 (ZEB2). A total of 50 gastric cancer tissues and their corresponding normal adjacent tissue samples were collected. Then, the expression levels of miR-200c and ZEB2 in both gastric cancer specimens and cells were detected using the quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical methods. A dual‑luciferase reporter gene assay was conducted to evaluate the effect of miR-200c on the 3'-untranslated region (3'UTR) luciferase activity of ZEB2. SGC7901/DDP cells were transfected with miR-200c mimics and ZEB2 siRNA, respectively. Subsequently, changes in cellular proliferation and apoptosis were detected through the methyl thiazolyl tetrazolium assay and flow cytometric analysis, respectively. We also carried out a western blot analysis assay in order to detect the expression of apoptosis-related genes and ZEB2. miR-200c was significantly downregulated and ZEB2 was significantly upregulated in both gastric cancer tissues and SGC7901/DDP cells when compared with those in normal tissues and SGC7901 cells (P<0.01). The dual luciferase reporter gene assay showed that miR-200c could specifically bind with the 3'UTR of ZEB2 and significantly suppress the luciferase activity by 42% (P<0.01). Upregulation of miR-200c or downregulation of ZEB2 enhanced the sensitivity of SGC7901/DDP cells to DDP. miR‑200c was significantly downregulated in both gastric cancer tissues and cells, while the expression of ZEB2 exhibited the opposite trend. Our study further demonstrated that miR-200c could enhance the sensitivity of SGC7901/DDP cells to DDP through targeted regulation of ZEB2 expression in gastric cancer tissues.
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing’s sarcoma gene (EWSR1) and the Wilms’ tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4) within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.