Death Effector Domain-containing Research Articles

JMJD6 functions as an oncogene and is associated with poor prognosis in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high prevalence and poor prognosis. It is an urgent problem to deeply understand the molecular mechanism of ESCC and develop effective diagnostic and prognostic methods.MethodsUsing tumor tissue and corresponding paracancerous samples from 141 resected ESCC patients, we assessed Jumonji domain-containing protein 6 (JMJD6) expression using Immunohistochemical (IHC) staining. Kaplan-Meier survival analysis and univariate or multivariate analysis were used to investigate the relationship between JMJD6 expression and clinicopathological features. The expression status and prognostic value of JMJD6 were analyzed by bioinformatics and enrichment analysis.ResultsThe expression of JMJD6 in ESCC samples was higher than that in the corresponding paracancerous samples, and high expression of JMJD6 was positively associated with poor prognosis of ESCC patients. In addition, bioinformatics analysis of the expression and prognosis of JMJD6 in a variety of tumors showed that high expression of JMJD6 was significantly associated with poor overall survival (OS) in ESCC patients. Enrichment analysis indicated that the high expression of genes similar to JMJD6, such as Conserved oligomeric Golgi 1(COG1), Major facilitator superfamily domain 11 (MFSD11) and Death Effector Domain Containing 2 (DEDD2), was associated with poor prognosis of ESCC, suggesting that JMJD6 might be involved in the occurrence and prognosis of ESCC.ConclusionOur study found that JMJD6 expression was significantly increased in ESCC patients and positively correlated with prognosis, indicating that targeting JMJD6 might be an attractive prognostic biomarker and provides a potential treatment strategy for ESCC.Trial registrationThe study was approved by Tangdu Hospital ethics committee (No. TDLL-202110-02).

Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell Line

Steroidal saponins are a group of compounds with complex structures and biological activities. They have anti-inflammatory, antimicrobial, fungicidal, and antitumor properties. Yamogenin is one of the spirostane saponins and occurs in Trigonella foenum-graecum, Asparagus officinalis, and Dioscorea collettii. It is a stereoisomer of diosgenin-a well-known compound whose activity and mechanisms of action in cancer cells are determined. However, the antitumor effect of yamogenin is still little known, and the mechanism of action has not been determined. In this study, we evaluated the effect of yamogenin on human ovarian cancer SKOV-3 cells in vitro by determining the cellular factors that trigger cell death. The viability of the cells was assessed with a Real-Time xCELLigence system and the cell cycle arrest with flow cytometry. The activity of initiator and executioner caspases (-8, -9, and -3/7) was estimated with luminometry and flow cytometry, respectively. The mitochondrial membrane depolarization, the level of oxidative stress, and DNA damage in the yamogenin-treated cells were also evaluated by flow cytometry. Genes expression analysis at the mRNA level was conducted with Real-Time PCR. Bid activation and chromatin condensation were estimated with fluorescent microscopy. The obtained results indicate that yamogenin has cytotoxic activity in SKOV-3 cells with an IC50 value of 23.90 ± 1.48 µg/mL and strongly inhibits the cell cycle in the sub-G1 phase. The compound also triggers cell death with a significant decrease in mitochondrial membrane potential, an increase in the level of oxidative stress (over two times higher in comparison to the control), and activation of caspase-8, -9, -3/7, as well as Bid. The results of genes expression indicate that the Tumor Necrosis Factor (TNF) Receptor Superfamily Members (TNF, TNFRSF10, TNFRSF10B, TNFRSF1B, and TNFRSF25), Fas Associated via Death Domain (FADD), and Death Effector Domain Containing 2 (DEDD2) were significantly upregulated and their relative expression was at least two times higher than in the control. Our work shows that yamogenin induces apoptosis in ovarian cancer cells, and both the extrinsic and mitochondrial-intrinsic pathways are involved in this process.

Long Non-Coding RNA Prostate Cancer Non-Coding RNA 1/miR-211-5p/Death Effector Domain Containing 2 Axis Affects Preeclampsia by Modulating Trophoblast Cells Proliferation and Apoptosis

Background: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that affects 5–7% of pregnant women and is characterized by edema, hypertension and proteinuria. It is one of the leading causes of morbidity and mortality in pregnant women and newborns. Evidences reveal that the expression of long non-coding RNA (lncRNA) prostate cancer non-coding RNA 1 (PRNCR1) is abnormal in PE. Therefore, we investigated the role of lncRNA PRNCR1 in PE development and its molecular mechanism. Methods: Quantitative reverse transcription PCR (qRT-PCR) was used to determine the expression levels of lncRNA PRNCR1, microRNA (miR)-211-5p and mRNA leval of death effector domain containing 2 (DEDD2). Besides, the expression level of DEDD2 was detected by western blot assay. Cell proliferation ability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, and cell apoptosis was detected by flow cytometry assay. Transwell assay was used to detect the migration and invasion of HTR-8/SVneo cells. The relationship between miR-211-5p and lncRNA PRNCR1 or DEDD2 was verified by dual luciferase reporter gene assay. Results: Over-expression of lncRNA PRNCR1 induced apoptosis, impeded proliferation, migration, invasion in HTR-8/SVneo cells. Knockdown of lncRNA PRNCR1 inhibited apoptosis, promoted cell proliferation, migration and invasion, and all these effects were offset by miR-211-5p inhibitor. The mRNA and protein levels of DEDD2 were decreased by overexpressing miR-211-5p in HTR-8/SVneo cells, while miR-211-5p inhibitor significantly increased the mRNA and protein levels of DEDD2. Conclusions: lncRNA PRNCR1 regulated cell behavior (proliferation, apoptosis, migration, and invasion) via the miR-211-5p/DEDD2 axis in HTR-8/SVneo cells. Thus, lncRNA PRNCR1 participated in the occurrence and development of PE.