Reduced expression of caspase-8 and cleaved caspase-3 in pancreatic ductal adenocarcinoma cells

Jakubowska, Katarzyna; Guzińska‐Ustymowicz, Katarzyna; Famulski, W; Cepowicz, Dariusz; Jagodzińska, D.; Pryczynicz, Anna

doi:10.3892/ol.2016.4125

Cited by 33 publications

(22 citation statements)

References 18 publications

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“…The caspase activation mechanism is a major signaling pathway leading to apoptosis 28 . Caspases are divided into effectors (such as caspases 3, 6, and 7) and initiators (such as caspases 8 and 9) 29 . The cleaved caspase 8 subsequently initiates apoptosis via proteolytic activation of downstream effector caspases 30 .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-21 Inhibits the Apoptosis of Osteosarcoma Cell Line SAOS-2 via Targeting Caspase 8

Xia

Cao

et al. 2017

oncol res

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Currently, multiple microRNAs (miRNAs) have been found to play vital roles in the pathogenesis of osteosarcoma. This study aimed to investigate the role of miR-21 in osteosarcoma. The level of miR-21 in 20 pairs of osteosarcoma and corresponding adjacent tissues was monitored by qPCR. Human osteosarcoma cell line SAOS-2 was transfected with either miR-21 mimic or miR-21 inhibitor, and then cell viability, survival, and apoptosis were measured by MTT, colony formation assay, and flow cytometry. A target of miR-21 was predicted by the microRNA.org database and verified in vitro by using luciferase reporter, qPCR, and Western blot analyses. Finally, cells were cotransfected with siRNA against caspase 8 and miR-21 inhibitor, and the apoptotic cell rate was determined again. Results showed that the mRNA level of miR-21 was highly expressed in osteosarcoma tissues compared with adjacent tissues. Overexpression of miR-21 improved cell viability and survival but suppressed apoptosis. Caspase 8 was a direct target of miR-21, and it was negatively regulated by miR-21. Moreover, miR-21 suppression attenuated caspase 8 silencing and induced the decrease in apoptosis. In conclusion, overexpression of miR-21 suppressed SAOS-2 cell apoptosis via directly targeting caspase 8.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-21 Inhibits the Apoptosis of Osteosarcoma Cell Line SAOS-2 via Targeting Caspase 8

Xia

Cao

et al. 2017

oncol res

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“…Caspase activation mechanism is an important signaling pathway causing apoptosis [21, 22]. The caspases are composed of effectors (caspase 3, 6, and 7) and initiators (caspase 8 and 9) [23, 24]. The cleaved caspase-8 subsequently promotes apoptosis via proteolytic activation of these downstream effectors [25, 26].…”

Section: Discussionmentioning

confidence: 99%

LncRNA MEG3 influences the proliferation and apoptosis of psoriasis epidermal cells by targeting miR-21/caspase-8

Jia

Zhang

Lü

et al. 2019

BMC Mol and Cell Biol

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BackgroundIt was reported that microRNA-21(miR-21) was differentially expressed in the keratinocytes of psoriasis patients, and it may influence the apoptosis and proliferation of cells. The role of lncRNA maternally expressed gene3 (MEG3), a competing endogenous RNAs of miR-21, in the progression of psoriasis remains unclear. We aimed to unfold the influence of MEG3 and miR-21 on the proliferation and apoptosis of psoriasis epidermal cells.Methods50μg/L TNF-α was used to treat HaCaTs and NHEKs cells for 24 h, and then different experiments were conducted. qRT-PCR were applied for measuring the mRNA level of MEG3, miR-2, and caspase-8, and the protein expression of caspase-8 was measured with western blotting. Flow cytometry was used for assessing apoptosis. Cell proliferation was detected using MTT and colony formation assays. Dual luciferase reporter assay was applied for confirming the binding site between MEG3 and miR-21, miR-21 and Caspase-8.ResultsA cell model for in vitro studying the role of MEG3 in psoriasis pathophysiology was established using HaCaT and HHEKs. MEG3 was significantly down-regulated in HaCaT, HHEKs, and psoriatic skin samples. MEG3 inhibits proliferation and promotes apoptosis of Activated-HaCaT (Act-HaCaT) and Activated-HHEKs (Act- HHEK) by regulating miR-21, and the binding site between MEG3 and miR-21 was identified. We also found that miR-21 could inhibit the level of caspase-8 and identified the binding site between caspase-8 and miR-21. Some down-stream proteins of caspase-8, Cleaved caspase-8, cytc, and apaf-1 were regulated by miR-21 and MEG3.ConclusionMEG3/miR-21 axis may regulate the expression of caspase-8, and further influence the proliferation and apoptosis of psoriasis keratinocyte, Act-HaCaT and Act- HHEK. Therefore, our findings may provide a new thought for the study of pathogenesis and treatment of psoriasis.

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“…However, the role of expression and activation of various caspases in tumorigenesis remains a double-edged sword. Low expression levels or inactivation of caspases frequently occur in cancer cells and make the cells resistant to microenvironmental stresses and treatments [ 19 , 20 ]. Conversely, the overexpression of caspases in dying cells may release growth-stimulating signals to allow the non-apoptotic tumor cells to proliferate and survive under stress conditions [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and prognosis of oral tongue squamous cell carcinoma

et al. 2017

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Apoptosis plays a dual role in cancer development and malignancy. The role of apoptosis-related caspases in cancer remains controversial, particularly in oral tongue squamous cell carcinoma (OTSCC). In this study, we examined the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 on tissue microarrays consisting of samples from 246 OTSCC patients by immunohistochemistry. Wilcoxon signed-rank test indicated that the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 in tumor tissues were significantly higher compared to those in adjacent normal tissues (all p<0.001). The expression level of caspase-8 in tumors was elevated in patients with lymph node invasion. Moreover, positive expression of cleaved caspase-3 was associated with shorter disease-free survival (DFS) in OTSCC patients with moderate differentiation and lymph node invasion. Combination of either positive cleaved caspase-3 or higher caspase-3 expression or both was associated with poor DFS. Interestingly, stratification analysis showed that co-expression levels of positive cleaved caspase-3 or/and higher caspase-3 were associated with better disease-specific survival in patients with advanced stages of the disease, such as large tumor size and lymph node invasion, whereas it was associated with poor DFS in OTSCC patients with moderate cell differentiation and small tumor size. Taken together, cleaved caspase-3 and caspase-3/8/9 could be biomarkers for tumorigenesis in OTSCC patients. The co-expression level of cleaved caspase-3 and caspase-3 might be a prognostic biomarker for OTSCC patients, particular in those patients with certain tumor stages and cell differentiation status.

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Reduced expression of caspase-8 and cleaved caspase-3 in pancreatic ductal adenocarcinoma cells

Cited by 33 publications

References 18 publications

MicroRNA-21 Inhibits the Apoptosis of Osteosarcoma Cell Line SAOS-2 via Targeting Caspase 8

MicroRNA-21 Inhibits the Apoptosis of Osteosarcoma Cell Line SAOS-2 via Targeting Caspase 8

LncRNA MEG3 influences the proliferation and apoptosis of psoriasis epidermal cells by targeting miR-21/caspase-8

Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and prognosis of oral tongue squamous cell carcinoma

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