IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43974-w.html
   My bibliography  Save this article

LncRNA MIR200CHG inhibits EMT in gastric cancer by stabilizing miR-200c from target-directed miRNA degradation

Author

Listed:
  • Yixiao Zhu

    (Sun Yat-sen University Cancer Center
    The Chinese University of Hong Kong
    Central South University)

  • Chengmei Huang

    (Sun Yat-sen University Cancer Center)

  • Chao Zhang

    (Sun Yat-sen University Cancer Center)

  • Yi Zhou

    (Sun Yat-sen University Cancer Center)

  • Enen Zhao

    (Sun Yat-sen University Cancer Center)

  • Yaxin Zhang

    (Sun Yat-sen University Cancer Center)

  • Xingyan Pan

    (Sun Yat-sen University Cancer Center)

  • Huilin Huang

    (Sun Yat-sen University Cancer Center)

  • Wenting Liao

    (Sun Yat-sen University Cancer Center)

  • Xin Wang

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong, Shenzhen)

Abstract

Gastric cancer (GC) is a heterogeneous disease, threatening millions of lives worldwide, yet the functional roles of long non-coding RNAs (lncRNAs) in different GC subtypes remain poorly characterized. Microsatellite stable (MSS)/epithelial-mesenchymal transition (EMT) GC is the most aggressive subtype associated with a poor prognosis. Here, we apply integrated network analysis to uncover lncRNA heterogeneity between GC subtypes, and identify MIR200CHG as a master regulator mediating EMT specifically in MSS/EMT GC. The expression of MIR200CHG is silenced in MSS/EMT GC by promoter hypermethylation, associated with poor prognosis. MIR200CHG reverses the mesenchymal identity of GC cells in vitro and inhibits metastasis in vivo. Mechanistically, MIR200CHG not only facilitates the biogenesis of its intronic miRNAs miR-200c and miR-141, but also protects miR-200c from target-directed miRNA degradation (TDMD) through direct binding to miR-200c. Our studies reveal a landscape of a subtype-specific lncRNA regulatory network, providing clinically relevant biological insights towards MSS/EMT GC.

Suggested Citation

  • Yixiao Zhu & Chengmei Huang & Chao Zhang & Yi Zhou & Enen Zhao & Yaxin Zhang & Xingyan Pan & Huilin Huang & Wenting Liao & Xin Wang, 2023. "LncRNA MIR200CHG inhibits EMT in gastric cancer by stabilizing miR-200c from target-directed miRNA degradation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43974-w
    DOI: 10.1038/s41467-023-43974-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43974-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43974-w?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. Rajnish A. Gupta & Nilay Shah & Kevin C. Wang & Jeewon Kim & Hugo M. Horlings & David J. Wong & Miao-Chih Tsai & Tiffany Hung & Pedram Argani & John L. Rinn & Yulei Wang & Pius Brzoska & Benjamin Kong, 2010. "Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis," Nature, Nature, vol. 464(7291), pages 1071-1076, April.
    2. Mahmoud Ghandi & Franklin W. Huang & Judit Jané-Valbuena & Gregory V. Kryukov & Christopher C. Lo & E. Robert McDonald & Jordi Barretina & Ellen T. Gelfand & Craig M. Bielski & Haoxin Li & Kevin Hu & , 2019. "Next-generation characterization of the Cancer Cell Line Encyclopedia," Nature, Nature, vol. 569(7757), pages 503-508, May.
    3. Claudia Carrieri & Laura Cimatti & Marta Biagioli & Anne Beugnet & Silvia Zucchelli & Stefania Fedele & Elisa Pesce & Isidre Ferrer & Licio Collavin & Claudio Santoro & Alistair R. R. Forrest & Piero , 2012. "Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat," Nature, Nature, vol. 491(7424), pages 454-457, November.
    4. Chenguang Gong & Lynne E. Maquat, 2011. "lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements," Nature, Nature, vol. 470(7333), pages 284-288, February.
    5. Francesco Ghini & Carmela Rubolino & Montserrat Climent & Ines Simeone & Matteo J. Marzi & Francesco Nicassio, 2018. "Endogenous transcripts control miRNA levels and activity in mammalian cells by target-directed miRNA degradation," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    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. Huaijun Wang & Tiantian Ye & Zilong Guo & Yilong Yao & Haifu Tu & Pengfei Wang & Yu Zhang & Yao Wang & Xiaokai Li & Bingchen Li & Haiyan Xiong & Xuelei Lai & Lizhong Xiong, 2024. "A double-stranded RNA binding protein enhances drought resistance via protein phase separation in rice," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Nadege Gitego & Bogos Agianian & Oi Wei Mak & Vasantha Kumar MV & Emily H. Cheng & Evripidis Gavathiotis, 2023. "Chemical modulation of cytosolic BAX homodimer potentiates BAX activation and apoptosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Manish Kumar & David Molkentine & Jessica Molkentine & Kathleen Bridges & Tongxin Xie & Liangpeng Yang & Andrew Hefner & Meng Gao & Reshub Bahri & Annika Dhawan & Mitchell J. Frederick & Sahil Seth & , 2021. "Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    4. Feng Wang & Yang Xu & Robert Wang & Beatrice Zhang & Noah Smith & Amber Notaro & Samantha Gaerlan & Eric Kutschera & Kathryn E. Kadash-Edmondson & Yi Xing & Lan Lin, 2023. "TEQUILA-seq: a versatile and low-cost method for targeted long-read RNA sequencing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. C. Megan Young & Laurent Beziaud & Pierre Dessen & Angela Madurga Alonso & Albert Santamaria-Martínez & Joerg Huelsken, 2023. "Metabolic dependencies of metastasis-initiating cells in female breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Feng Zhi & Qiang Wang & Lian Xue & Naiyuan Shao & Rong Wang & Danni Deng & Suinuan Wang & Xiwei Xia & Yilin Yang, 2015. "The Use of Three Long Non-Coding RNAs as Potential Prognostic Indicators of Astrocytoma," PLOS ONE, Public Library of Science, vol. 10(8), pages 1-14, August.
    7. Miquel Anglada-Girotto & Ludovica Ciampi & Sophie Bonnal & Sarah A. Head & Samuel Miravet-Verde & Luis Serrano, 2024. "In silico RNA isoform screening to identify potential cancer driver exons with therapeutic applications," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    8. Fei Li & Yizhe Wang & Inah Hwang & Ja-Young Jang & Libo Xu & Zhong Deng & Eun Young Yu & Yiming Cai & Caizhi Wu & Zhenbo Han & Yu-Han Huang & Xiangao Huang & Ling Zhang & Jun Yao & Neal F. Lue & Paul , 2023. "Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    10. Peike Sheng & Lu Li & Tianqi Li & Yuzhi Wang & Nicholas M. Hiers & Jennifer S. Mejia & Jossie S. Sanchez & Lei Zhou & Mingyi Xie, 2023. "Screening of Drosophila microRNA-degradation sequences reveals Argonaute1 mRNA’s role in regulating miR-999," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Isabel Espadas & Jenna L. Wingfield & Yoshihisa Nakahata & Kaushik Chanda & Eddie Grinman & Ilika Ghosh & Karl E. Bauer & Bindu Raveendra & Michael A. Kiebler & Ryohei Yasuda & Vidhya Rangaraju & Sath, 2024. "Synaptically-targeted long non-coding RNA SLAMR promotes structural plasticity by increasing translation and CaMKII activity," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    12. Wei Hu & Yangjun Wu & Qili Shi & Jingni Wu & Deping Kong & Xiaohua Wu & Xianghuo He & Teng Liu & Shengli Li, 2022. "Systematic characterization of cancer transcriptome at transcript resolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Adrià Fernández-Torras & Miquel Duran-Frigola & Martino Bertoni & Martina Locatelli & Patrick Aloy, 2022. "Integrating and formatting biomedical data as pre-calculated knowledge graph embeddings in the Bioteque," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    14. Kazuya Tsujita & Reiko Satow & Shinobu Asada & Yoshikazu Nakamura & Luis Arnes & Keisuke Sako & Yasuyuki Fujita & Kiyoko Fukami & Toshiki Itoh, 2021. "Homeostatic membrane tension constrains cancer cell dissemination by counteracting BAR protein assembly," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    15. Nishanth Ulhas Nair & Patricia Greninger & Xiaohu Zhang & Adam A. Friedman & Arnaud Amzallag & Eliane Cortez & Avinash Das Sahu & Joo Sang Lee & Anahita Dastur & Regina K. Egan & Ellen Murchie & Miche, 2023. "A landscape of response to drug combinations in non-small cell lung cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    16. Linhua Wang & Mirjana Maletic-Savatic & Zhandong Liu, 2022. "Region-specific denoising identifies spatial co-expression patterns and intra-tissue heterogeneity in spatially resolved transcriptomics data," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    17. Xiao Chen & Yinglu Li & Fang Zhu & Xinjing Xu & Brian Estrella & Manuel A. Pazos & John T. McGuire & Dimitris Karagiannis & Varun Sahu & Mustafo Mustafokulov & Claudio Scuoppo & Francisco J. Sánchez-R, 2023. "Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    18. Johanna Zerbib & Marica Rosaria Ippolito & Yonatan Eliezer & Giuseppina Feudis & Eli Reuveni & Anouk Savir Kadmon & Sara Martin & Sonia Viganò & Gil Leor & James Berstler & Julia Muenzner & Michael Mü, 2024. "Human aneuploid cells depend on the RAF/MEK/ERK pathway for overcoming increased DNA damage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    19. Ye-Lin Liang & Yuan Zhang & Xi-Rong Tan & Han Qiao & Song-Ran Liu & Ling-Long Tang & Yan-Ping Mao & Lei Chen & Wen-Fei Li & Guan-Qun Zhou & Yin Zhao & Jun-Yan Li & Qian Li & Sheng-Yan Huang & Sha Gong, 2022. "A lncRNA signature associated with tumor immune heterogeneity predicts distant metastasis in locoregionally advanced nasopharyngeal carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    20. Claudia Capparelli & Timothy J. Purwin & McKenna Glasheen & Signe Caksa & Manoela Tiago & Nicole Wilski & Danielle Pomante & Sheera Rosenbaum & Mai Q. Nguyen & Weijia Cai & Janusz Franco-Barraza & Ric, 2022. "Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:14:y:2023:i:1:d:10.1038_s41467-023-43974-w. 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.