scholarly journals HIF2α-Sp1 interaction mediates a deacetylation-dependent FVII- gene activation under hypoxic conditions in ovarian cancer cells

2012 ◽  
Vol 40 (12) ◽  
pp. 5389-5401 ◽  
Author(s):  
Shiro Koizume ◽  
Shin Ito ◽  
Etsuko Miyagi ◽  
Fumiki Hirahara ◽  
Yoshiyasu Nakamura ◽  
...  
2020 ◽  
Vol 21 (21) ◽  
pp. 8110 ◽  
Author(s):  
Laura R. Moffitt ◽  
Maree Bilandzic ◽  
Amy L. Wilson ◽  
Yiqian Chen ◽  
Mark D. Gorrell ◽  
...  

The treatment of ovarian cancer has not significantly changed in decades and it remains one of the most lethal malignancies in women. The serine protease dipeptidyl peptidase 4 (DPP4) plays key roles in metabolism and immunity, and its expression has been associated with either pro- or anti-tumour effects in multiple tumour types. In this study, we provide the first evidence that DPP4 expression and enzyme activity are uncoupled under hypoxic conditions in ovarian cancer cells. Whilst we identified strong up-regulation of DPP4 mRNA expression under hypoxic growth, the specific activity of secreted DPP4 was paradoxically decreased. Further investigation revealed matrix metalloproteinases (MMP)-dependent inactivation and proteolytic shedding of DPP4 from the cell surface, mediated by at least MMP10 and MMP13. This is the first report of uncoupled DPP4 expression and activity in ovarian cancer cells, and suggests a previously unrecognized, cell- and tissue-type-dependent mechanism for the regulation of DPP4 in solid tumours. Further studies are necessary to identify the functional consequences of DPP4 processing and its potential prognostic or therapeutic value.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ping Liu ◽  
Huiqiong Huang ◽  
Xiaorong Qi ◽  
Ce Bian ◽  
Meng Cheng ◽  
...  

LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro, followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer.


Oncogene ◽  
2019 ◽  
Vol 38 (45) ◽  
pp. 7089-7105 ◽  
Author(s):  
Youngjin Han ◽  
Boyun Kim ◽  
Untack Cho ◽  
In Sil Park ◽  
Se Ik Kim ◽  
...  

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  

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