IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31574-z.html
   My bibliography  Save this article

The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors

Author

Listed:
  • Jasmin Bartl

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf
    Institute of Zoology University of Hamburg)

  • Marco Zanini

    (Institut Curie, PSL Research University, CNRS UMR, INSERM
    Université Paris Sud, Université Paris-Saclay, CNRS UMR, INSERM U)

  • Flavia Bernardi

    (Institut Curie, PSL Research University, CNRS UMR, INSERM
    Université Paris Sud, Université Paris-Saclay, CNRS UMR, INSERM U)

  • Antoine Forget

    (Institut Curie, PSL Research University, CNRS UMR, INSERM
    Université Paris Sud, Université Paris-Saclay, CNRS UMR, INSERM U)

  • Lena Blümel

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Julie Talbot

    (Institut Curie, PSL Research University, CNRS UMR, INSERM
    Université Paris Sud, Université Paris-Saclay, CNRS UMR, INSERM U)

  • Daniel Picard

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Nan Qin

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Gabriele Cancila

    (Institut Curie, PSL Research University, CNRS UMR, INSERM
    Université Paris Sud, Université Paris-Saclay, CNRS UMR, INSERM U)

  • Qingsong Gao

    (St Jude Children’s Research Hospital)

  • Soumav Nath

    (Heinrich Heine University
    IBI- (Strukturbiochemie) and JuStruct, Forschungszentrum Jülich)

  • Idriss Mahoungou Koumba

    (Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf)

  • Marietta Wolter

    (Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • François Kuonen

    (Stanford University School of Medicine
    Lausanne University Hospital Center, CH- Lausanne)

  • Maike Langini

    (Heinrich Heine University)

  • Thomas Beez

    (Heinrich Heine University)

  • Christopher Munoz

    (Heinrich Heine University)

  • David Pauck

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Viktoria Marquardt

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Hua Yu

    (Institut Curie, PSL Research University, CNRS UMR, INSERM
    Université Paris Sud, Université Paris-Saclay, CNRS UMR, INSERM U)

  • Judith Souphron

    (Institut Curie, PSL Research University, CNRS UMR, INSERM
    Université Paris Sud, Université Paris-Saclay, CNRS UMR, INSERM U)

  • Mascha Korsch

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Christina Mölders

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Daniel Berger

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Sarah Göbbels

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Frauke-Dorothee Meyer

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Björn Scheffler

    (partner site University Hospital Essen)

  • Barak Rotblat

    (Ben-Gurion University of the Negev
    The National Institute for Biotechnology in the Negev)

  • Sven Diederichs

    (University of Freiburg, DKTK, partner site Freiburg
    Division of RNA Biology & Cancer, DKFZ)

  • Vijay Ramaswamy

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Hiromishi Suzuki

    (The Hospital for Sick Children)

  • Anthony Oro

    (Stanford University School of Medicine
    Stanford University)

  • Kai Stühler

    (Heinrich Heine University)

  • Anja Stefanski

    (Heinrich Heine University)

  • Ute Fischer

    (Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf)

  • Gabriel Leprivier

    (Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Dieter Willbold

    (Heinrich Heine University
    IBI- (Strukturbiochemie) and JuStruct, Forschungszentrum Jülich)

  • Gerhard Steger

    (Heinrich Heine University)

  • Alexander Buell

    (Technical University of Denmark)

  • Marcel Kool

    (Hopp Children´s Cancer Center (KiTZ)
    Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)
    Princess Máxima Center for Pediatric Oncology)

  • Peter Lichter

    (Division of Molecular Genetics, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), and National Center for Tumor Diseases (NCT))

  • Stefan M. Pfister

    (Hopp Children´s Cancer Center (KiTZ)
    Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)
    Heidelberg University Hospital)

  • Paul A. Northcott

    (St Jude Children’s Research Hospital)

  • Michael D. Taylor

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto
    The Hospital for Sick Children)

  • Arndt Borkhardt

    (Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf)

  • Guido Reifenberger

    (Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

  • Olivier Ayrault

    (Institut Curie, PSL Research University, CNRS UMR, INSERM
    Université Paris Sud, Université Paris-Saclay, CNRS UMR, INSERM U)

  • Marc Remke

    (Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, and DKTK, partner site Essen/Düsseldorf
    Heinrich Heine University, Düsseldorf, Germany, DKTK, partner site Essen/Düsseldorf)

Abstract

Most lncRNAs display species-specific expression patterns suggesting that animal models of cancer may only incompletely recapitulate the regulatory crosstalk between lncRNAs and oncogenic pathways in humans. Among these pathways, Sonic Hedgehog (SHH) signaling is aberrantly activated in several human cancer entities. We unravel that aberrant expression of the primate-specific lncRNA HedgeHog Interacting Protein-AntiSense 1 (HHIP-AS1) is a hallmark of SHH-driven tumors including medulloblastoma and atypical teratoid/rhabdoid tumors. HHIP-AS1 is actively transcribed from a bidirectional promoter shared with SHH regulator HHIP. Knockdown of HHIP-AS1 induces mitotic spindle deregulation impairing tumorigenicity in vitro and in vivo. Mechanistically, HHIP-AS1 binds directly to the mRNA of cytoplasmic dynein 1 intermediate chain 2 (DYNC1I2) and attenuates its degradation by hsa-miR-425-5p. We uncover that neither HHIP-AS1 nor the corresponding regulatory element in DYNC1I2 are evolutionary conserved in mice. Taken together, we discover an lncRNA-mediated mechanism that enables the pro-mitotic effects of SHH pathway activation in human tumors.

Suggested Citation

  • Jasmin Bartl & Marco Zanini & Flavia Bernardi & Antoine Forget & Lena Blümel & Julie Talbot & Daniel Picard & Nan Qin & Gabriele Cancila & Qingsong Gao & Soumav Nath & Idriss Mahoungou Koumba & Mariet, 2022. "The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31574-z
    DOI: 10.1038/s41467-022-31574-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31574-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31574-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Joan Massagué, 2004. "G1 cell-cycle control and cancer," Nature, Nature, vol. 432(7015), pages 298-306, November.
    2. Weiqi Zhang & Haifeng Wan & Guihai Feng & Jing Qu & Jiaqiang Wang & Yaobin Jing & Ruotong Ren & Zunpeng Liu & Linlin Zhang & Zhiguo Chen & Shuyan Wang & Yong Zhao & Zhaoxia Wang & Yun Yuan & Qi Zhou &, 2018. "SIRT6 deficiency results in developmental retardation in cynomolgus monkeys," Nature, Nature, vol. 560(7720), pages 661-665, August.
    3. Silvana Konermann & Mark D. Brigham & Alexandro E. Trevino & Julia Joung & Omar O. Abudayyeh & Clea Barcena & Patrick D. Hsu & Naomi Habib & Jonathan S. Gootenberg & Hiroshi Nishimasu & Osamu Nureki &, 2015. "Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex," Nature, Nature, vol. 517(7536), pages 583-588, January.
    4. Giles Robinson & Matthew Parker & Tanya A. Kranenburg & Charles Lu & Xiang Chen & Li Ding & Timothy N. Phoenix & Erin Hedlund & Lei Wei & Xiaoyan Zhu & Nader Chalhoub & Suzanne J. Baker & Robert Hueth, 2012. "Novel mutations target distinct subgroups of medulloblastoma," Nature, Nature, vol. 488(7409), pages 43-48, August.
    5. Nian Liu & Qing Dai & Guanqun Zheng & Chuan He & Marc Parisien & Tao Pan, 2015. "N6-methyladenosine-dependent RNA structural switches regulate RNA–protein interactions," Nature, Nature, vol. 518(7540), pages 560-564, February.
    6. Hiromichi Suzuki & Sachin A. Kumar & Shimin Shuai & Ander Diaz-Navarro & Ana Gutierrez-Fernandez & Pasqualino Antonellis & Florence M. G. Cavalli & Kyle Juraschka & Hamza Farooq & Ichiyo Shibahara & M, 2019. "Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma," Nature, Nature, vol. 574(7780), pages 707-711, October.
    7. Sebastian M. Waszak & Giles W, Robinson & Brian L. Gudenas & Kyle S. Smith & Antoine Forget & Marija Kojic & Jesus Garcia-Lopez & Jennifer Hadley & Kayla V. Hamilton & Emilie Indersie & Ivo Buchhalter, 2020. "Germline Elongator mutations in Sonic Hedgehog medulloblastoma," Nature, Nature, vol. 580(7803), pages 396-401, April.
    8. Esther Rheinbay & Prasanna Parasuraman & Jonna Grimsby & Grace Tiao & Jesse M. Engreitz & Jaegil Kim & Michael S. Lawrence & Amaro Taylor-Weiner & Sergio Rodriguez-Cuevas & Mara Rosenberg & Julian Hes, 2017. "Recurrent and functional regulatory mutations in breast cancer," Nature, Nature, vol. 547(7661), pages 55-60, July.
    9. Paul A. Northcott & Ivo Buchhalter & A. Sorana Morrissy & Volker Hovestadt & Joachim Weischenfeldt & Tobias Ehrenberger & Susanne Gröbner & Maia Segura-Wang & Thomas Zichner & Vasilisa A. Rudneva & Ha, 2017. "The whole-genome landscape of medulloblastoma subtypes," Nature, Nature, vol. 547(7663), pages 311-317, July.
    10. Jonathan J. Kotzin & Sean P. Spencer & Sam J. McCright & Dinesh B. Uthaya Kumar & Magalie A. Collet & Walter K. Mowel & Ellen N. Elliott & Asli Uyar & Michelle A. Makiya & Margaret C. Dunagin & Christ, 2016. "The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan," Nature, Nature, vol. 537(7619), pages 239-243, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Samuel Rivero-Hinojosa & Melanie Grant & Aswini Panigrahi & Huizhen Zhang & Veronika Caisova & Catherine M. Bollard & Brian R. Rood, 2021. "Proteogenomic discovery of neoantigens facilitates personalized multi-antigen targeted T cell immunotherapy for brain tumors," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Zaili Luo & Dazhuan Xin & Yunfei Liao & Kalen Berry & Sean Ogurek & Feng Zhang & Liguo Zhang & Chuntao Zhao & Rohit Rao & Xinran Dong & Hao Li & Jianzhong Yu & Yifeng Lin & Guoying Huang & Lingli Xu &, 2023. "Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Michelle M. Kameda-Smith & Helen Zhu & En-Ching Luo & Yujin Suk & Agata Xella & Brian Yee & Chirayu Chokshi & Sansi Xing & Frederick Tan & Raymond G. Fox & Ashley A. Adile & David Bakhshinyan & Kevin , 2022. "Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Ilia Kats & Milena Simovic-Lorenz & Hannah Sophia Schreiber & Pooja Sant & Jan-Philipp Mallm & Verena Körber & Albert Li & Pravin Velmurugan & Sophie Heuer & Luisa Kües & Frauke Devens & Martin Sill &, 2024. "Spatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Petr Smirnov & Moritz J. Przybilla & Milena Simovic-Lorenz & R. Gonzalo Parra & Hana Susak & Manasi Ratnaparkhe & John KL. Wong & Verena Körber & Jan-Philipp Mallm & George Philippos & Martin Sill & T, 2024. "Multi-omic and single-cell profiling of chromothriptic medulloblastoma reveals genomic and transcriptomic consequences of genome instability," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    6. Shweta Godbole & Hannah Voß & Antonia Gocke & Simon Schlumbohm & Yannis Schumann & Bojia Peng & Martin Mynarek & Stefan Rutkowski & Matthias Dottermusch & Mario M. Dorostkar & Andrey Korshunov & Thoma, 2024. "Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    7. Qiwen Su-Tobon & Jiayi Fan & Michael Goldstein & Kevin Feeney & Hongyuan Ren & Patrick Autissier & Peiyi Wang & Yingzi Huang & Udayan Mohanty & Jia Niu, 2025. "CRISPR-Hybrid: A CRISPR-Mediated Intracellular Directed Evolution Platform for RNA Aptamers," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    8. Heathcliff Dorado García & Fabian Pusch & Yi Bei & Jennifer Stebut & Glorymar Ibáñez & Kristina Guillan & Koshi Imami & Dennis Gürgen & Jana Rolff & Konstantin Helmsauer & Stephanie Meyer-Liesener & N, 2022. "Therapeutic targeting of ATR in alveolar rhabdomyosarcoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Chih-Hao Wang & Tadataka Tsuji & Li-Hong Wu & Cheng-Ying Yang & Tian Lian Huang & Mari Sato & Farnaz Shamsi & Yu-Hua Tseng, 2024. "Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Tiantian Jing & Dianhui Wei & Xiaoli Xu & Chengsi Wu & Lili Yuan & Yiwen Huang & Yizhen Liu & Yanyi Jiang & Boshi Wang, 2024. "Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    11. Xiangfeng Kong & Hainan Zhang & Guoling Li & Zikang Wang & Xuqiang Kong & Lecong Wang & Mingxing Xue & Weihong Zhang & Yao Wang & Jiajia Lin & Jingxing Zhou & Xiaowen Shen & Yinghui Wei & Na Zhong & W, 2023. "Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Jian Wang & Yuxi Teng & Ruihua Zhang & Yifei Wu & Lei Lou & Yusong Zou & Michelle Li & Zhong-Ru Xie & Yajun Yan, 2021. "Engineering a PAM-flexible SpdCas9 variant as a universal gene repressor," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    13. Yuwei Zhang & Jieyu Zhao & Xiaona Chen & Yulong Qiao & Jinjin Kang & Xiaofan Guo & Feng Yang & Kaixin Lyu & Yiliang Ding & Yu Zhao & Hao Sun & Chun-Kit Kwok & Huating Wang, 2024. "DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via m6A reader YTHDF1," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    14. Alexander Martinez-Fundichely & Austin Dixon & Ekta Khurana, 2022. "Modeling tissue-specific breakpoint proximity of structural variations from whole-genomes to identify cancer drivers," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    15. Boris Kantor & Bernadette O’Donovan & Joseph Rittiner & Dellila Hodgson & Nicholas Lindner & Sophia Guerrero & Wendy Dong & Austin Zhang & Ornit Chiba-Falek, 2024. "The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    16. Qichen Yuan & Hongzhi Zeng & Tyler C. Daniel & Qingzhuo Liu & Yongjie Yang & Emmanuel C. Osikpa & Qiaochu Yang & Advaith Peddi & Liliana M. Abramson & Boyang Zhang & Yong Xu & Xue Gao, 2024. "Orthogonal and multiplexable genetic perturbations with an engineered prime editor and a diverse RNA array," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    17. Ulrik Kristoffer Stoltze & Jon Foss-Skiftesvik & Thomas van Overeem Hansen & Simon Rasmussen & Konrad J. Karczewski & Karin A. W. Wadt & Kjeld Schmiegelow, 2024. "The evolutionary impact of childhood cancer on the human gene pool," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    18. David R. Ghasemi & Konstantin Okonechnikov & Anne Rademacher & Stephan Tirier & Kendra K. Maass & Hanna Schumacher & Piyush Joshi & Maxwell P. Gold & Julia Sundheimer & Britta Statz & Ahmet S. Rifaiog, 2024. "Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    19. Silvia Pomella & Matteo Cassandri & Lucrezia D’Archivio & Antonella Porrazzo & Cristina Cossetti & Doris Phelps & Clara Perrone & Michele Pezzella & Antonella Cardinale & Marco Wachtel & Sara Aloisi &, 2023. "MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57Kip2 targeting," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    20. Mahnaz Hosseinpour & Xinqi Xi & Ling Liu & Luis Malaver-Ortega & Laura Perlaza-Jimenez & Jihoon E. Joo & Harrison M. York & Jonathan Beesley & C. Elizabeth Caldon & Pierre-Antoine Dugué & James G. Dow, 2024. "SAM-DNMT3A, a strategy for induction of genome-wide DNA methylation, identifies DNA methylation as a vulnerability in ER-positive breast cancers," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31574-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.