The Role of Hypoxia-Induced miR-210 in Cancer Progression

Dang, Kyvan; Myers, Kenneth A.

doi:10.3390/ijms16036353

Cited by 140 publications

(125 citation statements)

References 100 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…This adaptation is correlated with tumor progression and poor prognosis (43,44). However, other recent work has identified the micro-RNA miR-210 as a "master" hypoxia-regulated miRNA, exhibiting up-regulation by HIF-1␣ under conditions of hypoxia (45)(46)(47). miR-210 promotes cell cycle progression and evasion of apoptosis while compromising mitochondrial integrity and DNA repair in numerous cancer cell lines (47).…”

Section: Discussionmentioning

confidence: 99%

“…However, other recent work has identified the micro-RNA miR-210 as a "master" hypoxia-regulated miRNA, exhibiting up-regulation by HIF-1␣ under conditions of hypoxia (45)(46)(47). miR-210 promotes cell cycle progression and evasion of apoptosis while compromising mitochondrial integrity and DNA repair in numerous cancer cell lines (47). Additional work is required to fully understand the complex interplay between miRNA biogenesis and hypoxia adaptation in human cells, as well as in fission yeast, which lack an HIF homolog.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mga2 Transcription Factor Regulates an Oxygen-responsive Lipid Homeostasis Pathway in Fission Yeast

Burr

Stewart

Shao

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Eukaryotic lipid synthesis is oxygen-dependent with cholesterol synthesis requiring 11 oxygen molecules and fatty acid desaturation requiring 1 oxygen molecule per double bond. Accordingly, organisms evaluate oxygen availability to control lipid homeostasis. The sterol regulatory element-binding protein (SREBP) transcription factors regulate lipid homeostasis. In mammals, SREBP-2 controls cholesterol biosynthesis, whereas SREBP-1 controls triacylglycerol and glycerophospholipid biosynthesis. In the fission yeast Schizosaccharomyces pombe, the SREBP-2 homolog Sre1 regulates sterol homeostasis in response to changing sterol and oxygen levels. However, notably missing is an SREBP-1 analog that regulates triacylglycerol and glycerophospholipid homeostasis in response to low oxygen. Consistent with this, studies have shown that the Sre1 transcription factor regulates only a fraction of all genes up-regulated under low oxygen. To identify new regulators of low oxygen adaptation, we screened the S. pombe nonessential haploid deletion collection and identified 27 gene deletions sensitive to both low oxygen and cobalt chloride, a hypoxia mimetic. One of these genes, mga2, is a putative transcriptional activator. In the absence of mga2, fission yeast exhibited growth defects under both normoxia and low oxygen conditions. Mga2 transcriptional targets were enriched for lipid metabolism genes, and mga2⌬ cells showed disrupted triacylglycerol and glycerophospholipid homeostasis, most notably with an increase in fatty acid saturation. Indeed, addition of exogenous oleic acid to mga2⌬ cells rescued the observed growth defects. Together, these results establish Mga2 as a transcriptional regulator of triacylglycerol and glycerophospholipid homeostasis in S. pombe, analogous to mammalian SREBP-1.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mga2 Transcription Factor Regulates an Oxygen-responsive Lipid Homeostasis Pathway in Fission Yeast

Burr

Stewart

Shao

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…A miR-210-et tekintik a fő hypoxia indukálta miRNS-nek (hypoxamiR). Elősegíti a tumoros folyamatok progreszszióját, befolyásolja a sejtciklus szabályozását, az apoptó-zist, a mitokondrium funkcióját, az angiogenezist és a sejtek metasztázisképző hajlamát is [28,29]. Célpontjai között például a sejtciklus szabályozásáért felelős E2F3 transzkripciós faktor, valamint az NFκB jelátvitel is szerepel.…”

Section: A Mir-210unclassified

“…Célpontjai között például a sejtciklus szabályozásáért felelős E2F3 transzkripciós faktor, valamint az NFκB jelátvitel is szerepel. Emelkedett szintjét számos daganatban, például gliomában, malignus melanomában, hasnyálmirigyrák-ban is leírták [24,28].…”

Section: A Mir-210unclassified

A mikro-RNS-ek patogenetikai és diagnosztikai szerepe mellékvesekéreg-carcinomában

et al. 2018

View full text Add to dashboard Cite

A mellékvesekéreg daganatos elváltozásai a népesség jelentős részét érintik. E daganatok többsége jóindulatú, hormonálisan inaktív mellékvesekéreg-adenoma. A ritka hormontermelő mellékvesekéreg-adenomák súlyos klinikai kö-vetkezményekkel járó betegségeket okoznak, a kifejezetten ritka mellékvesekéreg-carcinoma prognózisa ugyanakkor előrehaladott stádiumaiban nagyon rossz. E daganatok patogenezise a mai napig nem teljesen tisztázott. A mikro-RNS-ek kisméretű nem kódoló RNS-molekulák, amelyek a génexpresszió poszttranszkripciós szabályozása révén jelentős szerepet töltenek be számos alapvető sejtbiológiai folyamatban. Megváltozott kifejeződésüket számos daganatban leírták. Több szöveti mikro-RNS, így a miR-483-5p, a miR-503, a miR-210, a miR-335 és a miR-195 megváltozott kifejeződését találták jó-és rosszindulatú mellékvese-daganatok között, és ezeknek patogenetikai jelentősé-gük is lehet. A mikro-RNS-ek szövetspecifikus és stabil kifejeződésüknek köszönhetően a diagnosztikában is felhasználhatók lehetnek. Tekintettel arra, hogy a mellékvesekéreg-daganatok szövettani diagnózisa nehéz, a szöveti mikro-RNS-ek segíthetnek a malignitás megállapításában is. Új eredmények igazolták, hogy a mikro-RNS-ek külön-böző testnedvekbe is kiválasztódnak, ami a folyadékbiopszia módszere révén biomarkerként történő felhasználható-ságukat vetíti előre. Összefoglaló cikkünkben a mikro-RNS-ek mellékvesekéreg-daganatokban betöltött patogenetikai szerepét és diagnosztikai alkalmazási lehetőségeit tekintjük át. Orv Hetil. 2018; 159(7): 245-251. Kulcsszavak: mellékvesekéreg-rák, mikro-RNS, szöveti, keringő, extracellularis vesicula Pathogenic and diagnostic roles of microRNAs in adrenocortical tumoursAdrenocortical tumours are quite prevalent. Most of these tumours are benign, hormonally inactive adrenocortical adenomas. Rare hormone-secreting adrenocortical adenomas are associated with severe clinical consequences, whereas the prognosis of the rare adrenocortical cancer is rather poor in its advanced stages. The pathogenesis of these tumours is only partly elucidated. MicroRNAs are small, non-coding RNA molecules that are pivotal in the regulation of several basic cell biological processes via the posttranscriptional regulation of gene expression. Their altered expression has been described in many tumours. Several tissue microRNAs, such as miR- 483-5p, miR-503, miR-210, miR-335 and miR-195 were found to be differentially expressed among benign and malignant adrenocortical tumours, and these could also have pathogenic relevance. Due to their tissue specific and stable expression, microRNAs can be exploited in diagnostics as well. As the histological diagnosis of adrenocortical malignancy is difficult, microRNAs might be of help in the establishment of malignancy. Novel data show that microRNAs are secreted in various body fluids, projecting their applicability as biomarkers as part of liquid biopsy. In this review, we attempt to present a synopsis on the pathogenic relevance of microRNAs in adrenocortical tumours and their potential di...

show abstract

“…Moreover, miR-210 is strongly linked with the hypoxia pathway [13] and upregulated in response to hypoxia-inducible factors [14]. Recent research suggests that miR-210 additionally plays important roles in regulation of energy metabolism [15], immunity [16], cell proliferation and apoptosis [17].…”

Section: Introductionmentioning

confidence: 99%

The Favored Mechanism for Coping with Acute Cold Stress: Upregulation of miR-210 in Rats

Guo

Lian

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The main aim of this study was to determine the mechanisms by which rno-miR-210-3p affects changes in gene expression, metabolism, apoptosis and proliferation of cells under acute cold stress (ACS) conditions. Methods: The treatment group (n=6, weight 340±20 g) was exposed to ACS (temperature 4±0.5°C, relative humidity 45±0.5%) and the control group (n=6, weight 340±20 g) to normal temperature (NT) (temperature 24±0.5°C, relative humidity 45±0.5%). Rat liver samples were collected for qRT-PCR and western blot analyses to detect relative expression of rno-miR-210-3p, ISCU, Rap1b, ATP1b1, GPD1, E2F3, RAD52, PSMB6 and GPD2. For cell experiments, 100 pmol/dish rno-miR-210-3p mimic and 150 pmol/dish rno-miR-210-3p inhibitor were used. Mitochondrial glucose flux and glycolysis were measured using the XFe24 Extracellular Flux Analyzer. Cells were collected for apoptosis analysis 24 h after transfection and proliferation was quantified using the WST-1 Cell Proliferation and Cytotoxicity Assay Kit (Beyotime, Shanghai, China), according to the manufacturerʹs instructions. Results: In the rat experiment, expression of rno-miR-210-3p under ACS was increased sharply while ISCU, E2F3, RAD52, and PSMB6 levels declined, along with protein expression of ISCU and PSMB6. In cell experiments, ISCU, Rap1b, ATP1b1, GPD1, E2F3, RAD52, PSMB6 and GPD2 genes were downregulated while ISCU and PSMB6 protein expression decreased with upregulation of rno-miR-210-3p. Conversely, in response to decreased rno-miR-210-3p expression, ISCU, E2F3, RAD52, PSMB6 and GPD2 genes were upregulated, in addition to ISCU and PSMB6 proteins. Upregulation of miR-210 inhibited cell proliferation and induced cell death whereas its downregulation promoted cell proliferation. Upregulation or downregulation of miR-210 promoted glycolysis and mitochondrial respiration of BRL cells. However, downregulation of miR-210 caused acid production in cells. Conclusion: Expression of rno-miR-210-3p is significantly increased under ACS. Upregulation of rno-miR-210-3p inhibits the expression of ISCU, Rap1b, ATP1b1, GPD1, E2F3, RAD52, PSMB6 and GPD2 genes, promotes glycolysis of liver and enhances the mitochondrial respiratory capacity of cells, but may also cause cell death. Our findings collectively indicate that regulation of rno-miR-210-3p is a preferential mechanism of choice used by the body to cope with ACS.

show abstract

The Role of Hypoxia-Induced miR-210 in Cancer Progression

Cited by 140 publications

References 100 publications

Mga2 Transcription Factor Regulates an Oxygen-responsive Lipid Homeostasis Pathway in Fission Yeast

Mga2 Transcription Factor Regulates an Oxygen-responsive Lipid Homeostasis Pathway in Fission Yeast

A mikro-RNS-ek patogenetikai és diagnosztikai szerepe mellékvesekéreg-carcinomában

The Favored Mechanism for Coping with Acute Cold Stress: Upregulation of miR-210 in Rats

Contact Info

Product

Resources

About