Model for Osteosarcoma-9 as a potent factor in cell survival and resistance to apoptosis

Vourvouhaki, Ekaterini; Carvalho, C. S.; Aguiar, Paulo

doi:10.1103/physreve.76.011926

Cited by 9 publications

(7 citation statements)

References 12 publications

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“…Functionally, it has been implicated in ER-to-Golgi transport of the membrane protease and helps to select misfolded glycoproteins for degradation 18 , 19 . Recently, Carvalho and colleagues showed that OS-9 is involved in cell survival and resistance to apoptosis 20 . Should be note, the current studies suggested that OS-9 may affects hypoxic signaling via interaction with either the transcription factor HIF-1α or an HIF-1α-independent pathway 14 , 21 , 22 .…”

Section: Introductionmentioning

confidence: 99%

A Novel Role of OS-9 in the Maintenance of Intestinal Barrier Function from Hypoxia-induced Injury via p38-dependent Pathway

Sun¹,

Xu²,

Yu³

et al. 2015

Int. J. Biol. Sci.

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OS-9 is a lectin required for efficient ubquitination of glycosylated substrates of endoplasmic reticulum-associated degradation (ERAD). OS-9 has previously been implicated in ER-to-Golgi transport and transcription factor turnover. However, we know very little about other functions of OS-9 under endoplasmic reticulum stress. Here, we used gene knockdown and overexpression approaches to study the protective effect of OS-9 on intestinal barrier function of intestinal epithelial cell Caco-2 monolayer. We found that OS-9 attenuated intestinal epithelial barrier dysfunction under hypoxia through up-regulating occludin and claudin-1 protein expression. Furthermore, we showed that the up-regulation of occludin and claudin-1 induced by OS-9 was mediated by p38 and ERK1/2 phosphorylation and did not involve HIF-1α. In summary, our results demonstrate that OS-9 up-regulates occludin and claudin-1 by activating the MAP kinase (MAPK) pathway, and thus protects the epithelial barrier function of Caco-2 monolayer under hypoxia condition.

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Section: Introductionmentioning

confidence: 99%

A Novel Role of OS-9 in the Maintenance of Intestinal Barrier Function from Hypoxia-induced Injury via p38-dependent Pathway

Sun¹,

Xu²,

Yu³

et al. 2015

Int. J. Biol. Sci.

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“…OS‐9 overexpression reduced the protein levels of HIF‐1 α , and the degradation of OS‐9 mRNA leads to increased HIF‐mediated transcription under both normoxic and hypoxic conditions. OS‐9 is able to form a complex with HIF‐1 α and PHD2 or PHD3, promoting the hydroxylation of HIF‐1 α and subsequent proteasomal degradation 57,58 . The observed expression of OS‐9 in human tumours expressing elevated HIF levels points towards a potential dominant‐negative form of OS‐9 in tumours 18,57 .…”

Section: Regulation Of Hifmentioning

confidence: 99%

Hypoxia‐inducible factors – regulation, role and comparative aspects in tumourigenesis

Hansen

Kristensen

Law

et al. 2010

Vet Comparative Oncology

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Hypoxia-inducible factors (HIFs) play a key role in the cellular response experienced in hypoxic tumours, mediating adaptive responses that allow hypoxic cells to survive in the hostile environment. Identification and understanding of tumour hypoxia and the influence on cellular processes carries important prognostic information and may help identify potential hypoxia circumventing and targeting strategies. This review summarizes current knowledge on HIF regulation and function in tumour cells and discusses the aspects of using companion animals as comparative spontaneous cancer models. Spontaneous tumours in companion animals hold a great research potential for the evaluation and understanding of tumour hypoxia and in the development of hypoxia-targeting therapeutics.

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“…p53 has a key role in mediating cellular response to various stress signals, mainly by inducing or repressing a number of proteins that are involved in cancer cell cycle progression and apoptosis (14). Clinically, apoptotic resistance has become one of the greatest challenges in cancer therapy due to fierce resistance of tumor cells through various molecular mechanisms (15,16). Thus, underlying molecular mechanism of apoptotic resistance and exploring more efficacy target therapies are urgently required to improve the overall survival rate for patients with osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-124 suppresses growth and aggressiveness of osteosarcoma and inhibits TGF-β-mediated AKT/GSK-3β/SNAIL-1 signaling

Jiang

Zhang

2018

Mol Med Report

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Osteosarcoma is one of the most common malignant tumors in adolescent populations and the prognosis remains incompletely understand. Previous reports have demonstrated that microRNA‑124 (miR‑124) has inhibitory effects on various human malignancies and is associated with tumor progression. However, the clinical significance and potential mechanisms of miR‑124 in the progression of osteosarcoma is not clearly understood. In this study, the potential molecular mechanism of miR‑124 in osteosarcoma tumorigenesis, growth and aggressiveness was investigated. The growth, proliferation, apoptosis, migration and invasion of osteosarcoma cells were investigated following miR‑124 transfection were determined by colony formation assay, western blotting, immunofluorescence, migration/invasion assays and reverse transcription‑quantitative polymerase chain reaction. In vivo anti‑cancer effects of miR‑124 were analyzed by a tumor growth assay, immunohistochemistry and survival rate observations. The results demonstrated that miR‑124 transfection significantly decreased integrin expression in osteosarcoma cells, and further inhibited growth, proliferation, migration and invasion of osteosarcoma cells. Flow cytometry assays indicated that miR‑124 transfection attenuated apoptosis resistance of osteosarcoma to tunicamycin, potentially via the downregulation of P53 and Bcl‑2 apoptosis regulator expression. Mechanistic assays demonstrated that miR‑124 transfection suppressed TGF‑β expression in osteosarcoma. An animal study revealed that tumor growth was reduced in tumor cells transfected with miR‑124 compared with control cells, and the survival rate was prolonged in mice with miR‑124 transfected xenografts compared with control tumors. In conclusion, these results indicate that miR‑124 transection inhibits the growth and aggressive of osteosarcoma, potentially via suppression of TGF‑β‑mediated AKT/GSK‑3β/snail family transcriptional repressor 1 (SNAIL‑1) signaling, suggesting miR‑124 may be a potential anti‑cancer agent/target for osteosarcoma therapy.

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Model for Osteosarcoma-9 as a potent factor in cell survival and resistance to apoptosis

Cited by 9 publications

References 12 publications

A Novel Role of OS-9 in the Maintenance of Intestinal Barrier Function from Hypoxia-induced Injury via p38-dependent Pathway

A Novel Role of OS-9 in the Maintenance of Intestinal Barrier Function from Hypoxia-induced Injury via p38-dependent Pathway

Hypoxia‐inducible factors – regulation, role and comparative aspects in tumourigenesis

MicroRNA-124 suppresses growth and aggressiveness of osteosarcoma and inhibits TGF-β-mediated AKT/GSK-3β/SNAIL-1 signaling

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