ArticleNature communications2014
Hypoxia-mediated downregulation of miRNA biogenesis promotes tumour progression.
Erratum issuedOpen access · bronzeAbstract read
In one paragraph
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 104 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 2 pooled it
7.0field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 183 citations in OpenAlex.
- Tissue micro-RNAs associated with colorectal cancer prognosis: a systematic review.Molecular biology reports · 2021Pooled it
- micro-RNAs dependent regulation of DNMT and HIF1α gene expression in thrombotic disorders.Scientific reports · 2019Pooled it
- Review
- Enhancement of Therapeutic mRNA Translation in Cellular Stress Conditions.International journal of molecular sciences · 2026Review
- Regulatory Roles and Therapeutic Potential of miR-122-5p in Hypoxic-Ischemic Brain Injury: Comprehensive Review.Cell biochemistry and biophysics · 2025Review
- The FBXW7-KMT2 axis in cancer-associated fibroblasts controls tumor growth via an epigenetic-paracrine mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ambivalent roles of miRNAs in cancer development via modulating tumor-associated innate immune cells.BioImpacts : BI · 2025Review
- MicroRNAs in breast cancer-new frontiers in diagnosis, targeted therapy, and prognosis assessment.Frontiers in oncology · 2025Review
- Cancer metastases: Tailoring the targets.Heliyon · 2024Review
- miRNA Signatures in Bronchopulmonary Dysplasia: Implications for Biomarkers, Pathogenesis, and Therapeutic Options.Frontiers in bioscience (Landmark edition) · 2024Review
- Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.Advances in experimental medicine and biology · 2024Review
- Regulation of Cancer-Associated miRNAs Expression under Hypoxic Conditions.Analytical cellular pathology (Amsterdam) · 2024Review
- Inflammation and tumor microenvironment.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Review
- GATA6-AS1 suppresses epithelial-mesenchymal transition of pancreatic cancer under hypoxia through regulating SNAI1 mRNA stability.Journal of translational medicine · 2023Article
- Helicobacter pylori-activated fibroblasts as a silent partner in gastric cancer development.Cancer metastasis reviews · 2023Review
- MiRNA-Based Therapies for Lung Cancer: Opportunities and Challenges?Biomolecules · 2023Review
- Tumor-derived miRNAs as tumor microenvironment regulators for synergistic therapeutic options.Journal of cancer research and clinical oncology · 2023Review
- MicroRNA-185-5p: a marker of brain-sparing in foetuses with late-onset growth restriction.Epigenetics · 2022Article
- The Role of the Hypoxia-Related Unfolded Protein Response (UPR) in the Tumor Microenvironment.Cancers · 2022Review
- The Role of Non-Coding RNAs in Glioma.Biomedicines · 2022Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
29 authors at 1 institution in 1 country.
Rajesha Rupaimoole1] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Sherry Y WuDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Sunila PradeepDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Cristina Ivan1] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Chad V PecotDepartment of Molecular Therapeutics, University of North Carolina Lineberger Comprehensive Cancer Center, 101 Manning Drive, Chapel Hill, North Carolina 27599, USA.
Kshipra M Gharpure1] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Archana S Nagaraja1] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Guillermo N Armaiz-PenaDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Michael McGuireDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Behrouz ZandDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Heather J DaltonDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Justyna FilantDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Justin Bottsford MillerDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Chunhua LuDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Nouara C Sadaoui1] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Lingegowda S Mangala1] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Morgan TaylorDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Twan van den BeuckenDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 1L7.
Elizabeth Koch1] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 1L7 [2] Princess Margaret Cancer Centre and Campbell Family Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada M5G 1L7.
Cristian Rodriguez-Aguayo1] Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Li HuangDepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Menashe Bar-EliDepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Bradly G Wouters1] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 1L7 [2] Princess Margaret Cancer Centre and Campbell Family Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada M5G 1L7.
Milan RadovichDepartment of Surgery, Microbiology and Immunology, Indiana University, 980W Walnut Street, Indianapolis, Indiana 46202, USA.
Mircea IvanDepartment of Medicine, Microbiology and Immunology, Indiana University, 980W Walnut Street, Indianapolis, Indiana 46202, USA.
George A Calin1] Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Wei ZhangDepartment of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Gabriel Lopez-Berestein1] Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Anil K Sood1] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [2] Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA [3] Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
University of Toronto · CA
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MUNIVERSITY OF TEXAS MD ANDERSON SPORE IN OVARIAN CANCERP50CA083639 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BAST, ROBERT C · 1999 to 2015
$33.0MTargeting the PI3K Signaling Pathway in Endometrial CarcinomaP50CA098258 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BODURKA, DIANE · 2003 to 2020
$32.0MQuality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2MIndiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3MTexas Center for Cancer NanomedicineU54CA151668 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI FERRARI, MAURO · 2010 to 2014
$12.4MCenter for Systems Analysis of the Cancer RegulomeU24CA143835 · NCI · INSTITUTE FOR SYSTEMS BIOLOGY · PI SHMULEVICH, ILYA · 2009 to 2016
$10.6MTRAINING FOR ACADEMIC ONCOLOGY/HEMATOLOGYT32CA009666 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Michael Davies, Courtney DiNardo · 1994 to 2026
$9.8MTraining of Academic Gynecologic OncologistsT32CA101642 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ANIL K SOOD, Kathleen Schmeler · 2005 to 2026
$9.2MOvarian Cancer: Mechanisms of Neuroendocrine RegulationR01CA109298 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SOOD, ANIL K · 2005 to 2017
$4.5MPlatelets promote growth of ovarian cancerR01CA177909 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AFSHAR-KHARGHAN, VAHID, SOOD, ANIL K · 2013 to 2023
$4.1MTargeted therapeutics for ovarian cancer and its microenvironment - treatment and theoretical modelingU01CA213759 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LOPEZ-BERESTEIN, GABRIEL · 2017 to 2021
$2.5MCIHR 201592NCATS NIH HHS UH2 TR000943NCATS NIH HHS UH2TR000943NCATS NIH HHS UL1 TR001108NCI NIH HHS CA016672NCI NIH HHS CA109298NCI NIH HHS CA155332NCI NIH HHS CA177909NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA083639NCI NIH HHS P50 CA098258NCI NIH HHS R01 CA109298NCI NIH HHS R01 CA155332NCI NIH HHS R01 CA177909NCI NIH HHS T32 CA009666NCI NIH HHS T32 CA101642NCI NIH HHS U01 CA213759NCI NIH HHS U24 CA143835NCI NIH HHS U24CA143835NCI NIH HHS U54 CA151668
Abstract
Cancer-related deregulation of miRNA biogenesis has been suggested, but the underlying mechanisms remain elusive. Here we report a previously unrecognized effect of hypoxia in the downregulation of Drosha and Dicer in cancer cells that leads to dysregulation of miRNA biogenesis and increased tumour progression. We show that hypoxia-mediated downregulation of Drosha is dependent on ETS1/ELK1 transcription factors. Moreover, mature miRNA array and deep sequencing studies reveal altered miRNA maturation in cells under hypoxic conditions. At a functional level, this phenomenon results in increased cancer progression in vitro and in vivo, and data from patient samples are suggestive of miRNA biogenesis downregulation in hypoxic tumours. Rescue of Drosha by siRNAs targeting ETS1/ELK1 in vivo results in significant tumour regression. These findings provide a new link in the mechanistic understanding of global miRNA downregulation in the tumour microenvironment.
Indexed as
Disease ProgressionAnimalsCell HypoxiaCell Line, TumorDEAD-box RNA HelicasesDown-RegulationEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansMice, NudeMicroRNAsModels, BiologicalNeoplasmsProto-Oncogene Protein c-ets-1Ribonuclease IIIDEAD-box RNA HelicasesDICER1 protein, humanDROSHA protein, humanETS1 protein, humanMicroRNAsProto-Oncogene Protein c-ets-1Ribonuclease IIIVascular Endothelial Growth Factor A
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