Hypoxia-induced overexpression of DEC1 is regulated by HIF-1α in hepatocellular carcinoma.
TLDR
It is suggested that hypoxia induced the overexpression of DEC1, the mechanism of which may be related to the upregulation of HIF-1 α in HCC and the efficacy of inhibiting Hif-1α and DEC1 expression as a possible treatment for HCC should be assessed in clinical trials.Abstract:
Hypoxia-inducible factor-1α (HIF-1α) and differentiated embryo-chondrocyte expressed gene 1 (DEC1) are two key factors that protect hepatocellular carcinoma (HCC) cells from a hypoxic microenvironment. However, little is known concerning the effects of hypoxia on the expression of HIF-1α and DEC1 in HCC. In the present study, RT-PCR and western blotting were conducted to assay the mRNA and protein levels of HIF-1α and DEC1 under normoxia and hypoxia induced by exposure to CoCl2 for different time periods (0, 2, 4, 6, 24 and 48 h). In addition, the HIF-1α protein inhibitor, YC-1, was used to analyze the interaction between DEC1 and HIF-1α expression and the related mechanism. Results showed that expression of DEC1 in HCC was significantly upregulated at both the mRNA and protein levels, when compared with that in normal liver cells (P 0.05). A positive correlation was found between HIF-1α and DEC1 expression in both BEL-7402 (r=0.885, P<0.05) and SMMC-7721 cells (r=0.826, P<0.05). Furthermore, inhibition of HIF-1α by YC-1 led to a significant decrease in DEC1 induced by hypoxia (P<0.05). We suggest that hypoxia induced the overexpression of DEC1, the mechanism of which may be related to the upregulation of HIF-1α in HCC. The efficacy of inhibiting HIF-1α and DEC1 expression as a possible treatment for HCC should be assessed in clinical trials.read more
Citations
More filters
Journal ArticleDOI
The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality
Chaofan Li,Bibo Zhu,Young Min Son,Zheng Wang,Li Jiang,Min Xiang,Zhenqing Ye,Kathryn E. Beckermann,Yue Wu,James Jenkins,Peter J. Siska,Peter J. Siska,Benjamin G. Vincent,Y. S. Prakash,Tobias Peikert,Brian T. Edelson,Reshma Taneja,Mark H. Kaplan,Jeffrey C. Rathmell,Haidong Dong,Taro Hitosugi,Jie Sun +21 more
TL;DR: An epigenetic and metabolic regimen was identified that promoted Trm cell and TIL gene signatures associated with tissue residency and polyfunctionality and empowered the anti-tumor activity of CD8+ T cells and possessed therapeutic potential even at an advanced tumor stage in mouse models.
Journal ArticleDOI
YC-1 induces G0/G1 phase arrest and mitochondria-dependent apoptosis in cisplatin-resistant human oral cancer CAR cells.
Miau Rong Lee,Chingju Lin,Chi Cheng Lu,Sheng-Chu Kuo,Je Wei Tsao,Yu‑Ning Juan,Hong‑Yi Chiu,Fang Yu Lee,Jai Sing Yang,Fuu Jen Tsai +9 more
TL;DR: YC-1 suppressed the viability of cisplatin-resistant CAR cells through inhibiting cell proliferation, arresting cell cycle at G0/G1 phase and triggering mitochondria-mediated apoptosis.
Journal ArticleDOI
The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1
Cristina Gallo,Valentina Fragliasso,Benedetta Donati,Federica Torricelli,Annalisa Tameni,Simonetta Piana,Alessia Ciarrocchi +6 more
TL;DR: It is shown that DEC1 more than DEC2 sustains progression of thyroid cancer by promoting cell growth and invasiveness and thatDEC1 drives the expression of many cell cycle-related genes, uncovering a potential new function for this transcription factor in cancer.
Book ChapterDOI
Stra13 and Sharp-1, the non-grouchy regulators of development and disease.
TL;DR: Current understanding of Stra13 and Sharp-1 cellular functions that suggest a requirement in maintenance of tissue homeostasis are reviewed.
Journal ArticleDOI
Non-circadian aspects of BHLHE40 cellular function in cancer.
TL;DR: BHLHE40 is a multi-functional protein that mediates the promotion or suppression of cancer in a context dependent manner and may have different impacts on tumorigenesis.
References
More filters
Journal ArticleDOI
Levels of Hypoxia-Inducible Factor-1α During Breast Carcinogenesis
Reinhard Bos,Hua Zhong,Colleen F. Hanrahan,Ellen C. M. Mommers,Gregg L. Semenza,Herbert M. Pinedo,Martin D. Abeloff,Jonathan W. Simons,Paul J. van Diest,Elsken van der Wall +9 more
TL;DR: In this paper, the authors investigated whether the level of HIF-1α is increased during carcinogenesis in breast tissue and is associated with other tumor biomarkers, such as vascular endothelial growth factor (VEGF), HER-2/neu, p53, Ki-67, and estrogen receptor (ER).
Journal ArticleDOI
Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators
TL;DR: Differences between hypoxic and non-hypoxic induction and activation of Hif-1 are focused on and the biological functions of HIF-1 associated with these two induction pathways are discussed.
Journal ArticleDOI
Hypoxia inducible factors in cancer stem cells
John M. Heddleston,Zong-Ming Li,Justin D. Lathia,Shideng Bao,Anita B. Hjelmeland,Jeremy N. Rich +5 more
TL;DR: The current experimental evidence suggests that CSCs are plastic cell states governed by microenvironmental conditions that may be critical for the development of new therapies targeted to disrupt the microenvironment.
Journal ArticleDOI
Regulation of Metabolism by Hypoxia-Inducible Factor 1
TL;DR: A mechanism by which PKM2 promotes metabolic reprogramming is provided and it is suggested that it plays a broader role in cancer progression than has previously been appreciated.
Journal ArticleDOI
Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling.
Charles C. Wykoff,Christopher W. Pugh,Patrick H. Maxwell,Adrian L. Harris,Peter J. Ratcliffe +4 more
TL;DR: It is postulate that co-ordinate regulation as part of the HIF pathway may explain this paradox, and that evolution of anti-apoptotic pathways may be required for tumour growth under VHL-dysregulation.