Intracellular redox potential is correlated with miRNA expression in MCF7 cells under hypoxic conditions

[en] Hypoxia is a ubiquitous feature of cancers, encouraging glycolytic metabolism, proliferation, and resistance to therapy. Nonetheless, hypoxia is a poorly defined term with confounding features described in the literature. Redox biology provides an important link between the external cellular microenvironment and the cell's response to changing oxygen pressures. In this paper, we demonstrate a correlation between intracellular redox potential (measured using optical nanosensors) and the concentrations of microRNAs (miRNAs) involved in the cell's response to changes in oxygen pressure. The correlations were established using surprisal analysis (an approach derived from thermodynamics and information theory). We found that measured redox potential changes reflect changes in the free energy computed by surprisal analysis of miRNAs. Furthermore, surprisal analysis identified groups of miRNAs, functionally related to changes in proliferation and metastatic potential that played the most significant role in the cell's response to changing oxygen pressure. © 2019 National Academy of Sciences. All rights reserved.

Research Center/Unit :

MolSys - Molecular Systems - ULiège

Disciplines :

Physical, chemical, mathematical & earth Sciences: Multidisciplinary, general & others

Author, co-author :

Johnston, Hannah E.; School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, United Kingdom

Dickinson, Paul; Institute of Infection and Immunology Research, University of Edinburgh, Edinburgh, EH9 3FL, United Kingdom

Ivens, Alasdair C.; Institute of Infection and Immunology Research, University of Edinburgh, Edinburgh, EH9 3FL, United Kingdom

Buck, Amy H.; Institute of Infection and Immunology Research, University of Edinburgh, Edinburgh, EH9 3FL, United Kingdom

Levine, Raphaël David; Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 91904, Israel

Remacle, Françoise ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de chimie physique théorique

Campbell, Colin J.; School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, United Kingdom

Language :

English

Title :

Intracellular redox potential is correlated with miRNA expression in MCF7 cells under hypoxic conditions

Publication date :

2019

Journal title :

Proceedings of the National Academy of Sciences of the United States of America

ISSN :

0027-8424

eISSN :

1091-6490

Publisher :

National Academy of Sciences

Volume :

116

Issue :

Pages :

19753-19759

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

Medical Research Scotland
F.R.S.-FNRS - Fonds de la Recherche Scientifique
Leverhulme Trust

Available on ORBi :

since 05 January 2020

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Bibliography

D. Hanahan, R. A. Weinberg, Hallmarks of cancer: The next generation. Cell 144, 646-674 (2011).
G. L. Semenza, Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 29, 625-634 (2010).
C. Ward et al., New strategies for targeting the hypoxic tumour microenvironment in breast cancer. Cancer Treat. Rev. 39, 171-179 (2013).
V. L. Camus, G. D. Stewart, W. H. Nailon, D. B. McLaren, C. J. Campbell, Measuring the effects of fractionated radiation therapy in a 3D prostate cancer model system using SERS nanosensors. Analyst 141, 5056-5061 (2016). Erratum in: Analyst 141, 5900 (2016).
M. W. Dewhirst, Y. Cao, B. Moeller, Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat. Rev. Cancer 8, 425-437 (2008).
N. S. Chandel, M. G. Vander Heiden, C. B. Thompson, P. T. Schumacker, Redox regulation of p53 during hypoxia. Oncogene 19, 3840-3848 (2000).
J. Jiang, C. Auchinvole, K. Fisher, C. J. Campbell, Quantitative measurement of redox potential in hypoxic cells using SERS nanosensors. Nanoscale 6, 12104-12110 (2014).
G. L. Semenza, N. R. Prabhakar, Neural regulation of hypoxia-inducible factors and redox state drives the pathogenesis of hypertension in a rodent model of sleep apnea. J. Appl. Physiol. 119, 1152-1156 (2015).
D. Xie, T. L. King, A. Banerjee, V. Kohli, E. L. Que, Exploiting copper redox for 19F magnetic resonance-based detection of cellular hypoxia. J. Am. Chem. Soc. 138, 2937-2940 (2016).
J. Ye et al., Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discov. 4, 1406-1417 (2014).
P. Li et al., Redox homeostasis protects mitochondria through accelerating ROS conversion to enhance hypoxia resistance in cancer cells. Sci. Rep. 6, 22831 (2016).
S. R. McKeown, Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response. Br. J. Radiol. 87, 20130676 (2014).
V. Mallikarjun, D. J. Clarke, C. J. Campbell, Cellular redox potential and the biomolecular electrochemical series: A systems hypothesis. Free Radic. Biol. Med. 53, 280-288 (2012).
C. A. Auchinvole et al., Monitoring intracellular redox potential changes using SERS nanosensors. ACS Nano 6, 888-896 (2012).
K. M. Fisher et al., SERS as a tool for in vitro toxicology. Faraday Discuss. 187, 501-520 (2016).
L. E. Jamieson et al., Targeted SERS nanosensors measure physicochemical gradients and free energy changes in live 3D tumor spheroids. Nanoscale 8, 16710-16718 (2016).
L. E. Jamieson et al., Simultaneous intracellular redox potential and pH measurements in live cells using SERS nanosensors. Analyst (Lond.) 140, 2330-2335 (2015).
A. Jaworska et al., SERS-based monitoring of the intracellular pH in endothelial cells: The influence of the extracellular environment and tumour necrosis factor-α. Analyst 140, 2321-2329 (2015).
R. D. Levine, R. B. Bernstein, Energy disposal and energy consumption in elementary chemical reactions: Information theoretic approach. Acc. Chem. Res. 7, 393-400 (1974).
G. H. Golub, C. Reinsch, Singular value decomposition and least squares solutions. Numer. Math. 14, 403-420 (1970).
I. Procaccia, R. D. Levine, Potential work: A statistical-mechanical approach for systems in disequilibrium. J. Chem. Phys. 65, 3357 (1976).
M. A. Ochsenkühn, P. R. Jess, H. Stoquert, K. Dholakia, C. J. Campbell, Nanoshells for surface-enhanced Raman spectroscopy in eukaryotic cells: Cellular response and sensor development. ACS Nano 3, 3613-3621 (2009).
S. Nallamshetty, S. Y. Chan, J. Loscalzo, Hypoxia: A master regulator of microRNA biogenesis and activity. Free Radic. Biol. Med. 64, 20-30 (2013).
D. Ren et al., Oncogenic MIR-210-3p promotes prostate cancer cell EMT and bone metastasis via NF-kB signaling pathway. Mol. Cancer 16, 117 (2017).
J. M. Hernandez et al., MIR-675 mediates downregulation of Twist1 and Rb in AFPsecreting hepatocellular carcinoma. Ann. Surg. Oncol. 20 (suppl. 3), S625-S635 (2013).
K. Wu, L. Ma, J. Zhu, MIR-483-5p promotes growth, invasion and self-renewal of gastric cancer stem cells by Wnt/β-catenin signaling. Mol. Med. Rep. 14, 3421-3428 (2016).
Q. Zhang, S. Zhao, X. Pang, B. Chi, MicroRNA-381 suppresses cell growth and invasion by targeting the liver receptor homolog-1 in hepatocellular carcinoma. Oncol. Rep. 35, 1831-1840 (2016).
X. Shi et al., MIR-381 regulates neural stem cell proliferation and differentiation via regulating hes1 expression. PLoS One 10, e0138973 (2015).
B. T. Kaymaz et al., Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted "hsa-MIR-2278" as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A. Tumour Biol. 36, 7915-7927 (2015).
C. Lou et al., MIR-485-3p and MIR-485-5p suppress breast cancer cell metastasis by inhibiting PGC-1α expression. Cell Death Dis. 7, e2159 (2016).
G. X. Guo, Q. Y. Li, W. L. Ma, Z. H. Shi, X. Q. Ren, MicroRNA-485-5p suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting stanniocalcin 2. Int. J. Clin. Exp. Pathol. 8, 12292-12299 (2015).
A. Gross, R. D. Levine, Surprisal analysis of transcripts expression levels in the presence of noise: A reliable determination of the onset of a tumor phenotype. PLoS One 8, e61554 (2013).
F. Remacle, N. Kravchenko-Balasha, A. Levitzki, R. D. Levine, Information-theoretic analysis of phenotype changes in early stages of carcinogenesis. Proc. Natl. Acad. Sci. U.S.A. 107, 10324-10329 (2010).
W. Wei et al., Hypoxia induces a phase transition within a kinase signaling network in cancer cells. Proc. Natl. Acad. Sci. U.S.A. 110, E1352-E1360 (2013).
L. Marignol, M. Coffey, M. Lawler, D. Hollywood, Hypoxia in prostate cancer: A powerful shield against tumour destruction? Cancer Treat. Rev. 34, 313-327 (2008).
N. Kravchenko-Balasha et al., Convergence of logic of cellular regulation in different premalignant cells by an information theoretic approach. BMC Syst. Biol. 5, 42 (2011).
Cutadapt, Version 2.4. https://cutadapt.readthedocs.io/en/stable/. Accessed 4 September 2019.
MIRDeep2, Version 0.1.2. https://github.com/rajewsky-lab/MIRdeep2/releases/tag/ v0.1.2. Accessed 4 September 2019.
N. Kravchenko-Balasha et al., On a fundamental structure of gene networks in living cells. Proc. Natl. Acad. Sci. U.S.A. 109, 4702-4707 (2012).