IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50987-6.html
   My bibliography  Save this article

SNORD88B-mediated WRN nucleolar trafficking drives self-renewal in liver cancer initiating cells and hepatocarcinogenesis

Author

Listed:
  • Yang Gu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhibin Yi

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ziheng Zhou

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jianyi Wang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shan Li

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Pingping Zhu

    (Zhengzhou University)

  • Nian Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yuwei Xu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Lei He

    (PLA General Hospital)

  • Yanying Wang

    (Chinese Academy of Sciences
    Beijing Normal University)

  • Zusen Fan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Whether small nucleolar RNAs (snoRNAs) are involved in the regulation of liver cancer stem cells (CSCs) self-renewal and serve as therapeutic targets remains largely unclear. Here we show that a functional snoRNA (SNORD88B) is robustly expressed in Hepatocellular carcinoma (HCC) tumors and liver CSCs. SNORD88B deficiency abolishes the self-renewal of liver CSCs and hepatocarcinogenesis. Mechanistically, SNORD88B anchors WRN in the nucleolus, promoting XRCC5 interacts with STK4 promoter to suppress its transcription, leading to inactivation of Hippo signaling. Moreover, low expression of STK4 and high expression of XRCC5 are positively correlated with HCC poor prognosis. Additionally, snord88b knockout suppresses mouse liver tumorigenesis. Notably, co-administration of SNORD88B antisense oligonucleotides (ASOs) with MST1 agonist adapalene (ADA) exert synergistic antitumor effects and increase overall murine survival. Our findings delineate that SNORD88B drives self-renewal of liver CSCs and accelerates HCC tumorigenesis via non-canonical mechanism, providing potential targets for liver cancer therapy by eliminating liver CSCs.

Suggested Citation

  • Yang Gu & Zhibin Yi & Ziheng Zhou & Jianyi Wang & Shan Li & Pingping Zhu & Nian Liu & Yuwei Xu & Lei He & Yanying Wang & Zusen Fan, 2024. "SNORD88B-mediated WRN nucleolar trafficking drives self-renewal in liver cancer initiating cells and hepatocarcinogenesis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50987-6
    DOI: 10.1038/s41467-024-50987-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50987-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50987-6?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. Soufiane Boumahdi & Gregory Driessens & Gaelle Lapouge & Sandrine Rorive & Dany Nassar & Marie Le Mercier & Benjamin Delatte & Amélie Caauwe & Sandrine Lenglez & Erwin Nkusi & Sylvain Brohée & Isabell, 2014. "SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma," Nature, Nature, vol. 511(7508), pages 246-250, July.
    2. Pingping Zhu & Yanying Wang & Jiayi Wu & Guanling Huang & Benyu Liu & Buqing Ye & Ying Du & Guangxia Gao & Yong Tian & Lei He & Zusen Fan, 2016. "LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    3. Corbin E. Meacham & Sean J. Morrison, 2013. "Tumour heterogeneity and cancer cell plasticity," Nature, Nature, vol. 501(7467), pages 328-337, 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. Remy Elbez & Jeff Folz & Alan McLean & Hernan Roca & Joseph M Labuz & Kenneth J Pienta & Shuichi Takayama & Raoul Kopelman, 2021. "Cell-morphodynamic phenotype classification with application to cancer metastasis using cell magnetorotation and machine-learning," PLOS ONE, Public Library of Science, vol. 16(11), pages 1-14, November.
    2. Humberto Contreras-Trujillo & Jiya Eerdeng & Samir Akre & Du Jiang & Jorge Contreras & Basia Gala & Mary C. Vergel-Rodriguez & Yeachan Lee & Aparna Jorapur & Areen Andreasian & Lisa Harton & Charles S, 2021. "Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Seong Eun Lee & Seongyeol Park & Shinae Yi & Na Rae Choi & Mi Ae Lim & Jae Won Chang & Ho-Ryun Won & Je Ryong Kim & Hye Mi Ko & Eun-Jae Chung & Young Joo Park & Sun Wook Cho & Hyeong Won Yu & June You, 2024. "Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Bowen Li & Jianwu Tian & Fu Zhang & Chongzhi Wu & Zhiyao Li & Dandan Wang & Jiahao Zhuang & Siqin Chen & Wentao Song & Yufu Tang & Yuan Ping & Bin Liu, 2024. "Self-assembled aldehyde dehydrogenase-activatable nano-prodrug for cancer stem cell-enriched tumor detection and treatment," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Haralampos Hatzikirou & Nikos I. Kavallaris & Marta Leocata, 2021. "A Novel Averaging Principle Provides Insights in the Impact of Intratumoral Heterogeneity on Tumor Progression," Mathematics, MDPI, vol. 9(20), pages 1-27, October.
    6. Albert H Gough & Ning Chen & Tong Ying Shun & Timothy R Lezon & Robert C Boltz & Celeste E Reese & Jacob Wagner & Lawrence A Vernetti & Jennifer R Grandis & Adrian V Lee & Andrew M Stern & Mark E Schu, 2014. "Identifying and Quantifying Heterogeneity in High Content Analysis: Application of Heterogeneity Indices to Drug Discovery," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-16, July.
    7. Yanying Wang & Jing Wang & Xiaoyu Li & Xushen Xiong & Jianyi Wang & Ziheng Zhou & Xiaoxiao Zhu & Yang Gu & Dan Dominissini & Lei He & Yong Tian & Chengqi Yi & Zusen Fan, 2021. "N1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    8. Miranda V. Hunter & Reuben Moncada & Joshua M. Weiss & Itai Yanai & Richard M. White, 2021. "Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    9. Mingsen Li & Huaxing Huang & Bofeng Wang & Shaoshuai Jiang & Huizhen Guo & Liqiong Zhu & Siqi Wu & Jiafeng Liu & Li Wang & Xihong Lan & Wang Zhang & Jin Zhu & Fuxi Li & Jieying Tan & Zhen Mao & Chunqi, 2022. "Comprehensive 3D epigenomic maps define limbal stem/progenitor cell function and identity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Josefine Radke & Elisa Schumann & Julia Onken & Randi Koll & Güliz Acker & Bohdan Bodnar & Carolin Senger & Sascha Tierling & Markus Möbs & Peter Vajkoczy & Anna Vidal & Sandra Högler & Petra Kodajova, 2022. "Decoding molecular programs in melanoma brain metastases," Nature Communications, Nature, vol. 13(1), pages 1-24, December.
    11. Claudia Bühnemann & Simon Li & Haiyue Yu & Harriet Branford White & Karl L Schäfer & Antonio Llombart-Bosch & Isidro Machado & Piero Picci & Pancras C W Hogendoorn & Nicholas A Athanasou & J Alison No, 2014. "Quantification of the Heterogeneity of Prognostic Cellular Biomarkers in Ewing Sarcoma Using Automated Image and Random Survival Forest Analysis," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-14, September.
    12. Jacob C Kimmel & Amy Y Chang & Andrew S Brack & Wallace F Marshall, 2018. "Inferring cell state by quantitative motility analysis reveals a dynamic state system and broken detailed balance," PLOS Computational Biology, Public Library of Science, vol. 14(1), pages 1-29, January.
    13. Zhenzhen Chen & Qiankun He & Tiankun Lu & Jiayi Wu & Gaoli Shi & Luyun He & Hong Zong & Benyu Liu & Pingping Zhu, 2023. "mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. Jing Gao & Xingyu Jiang & Shumin Lei & Wenhao Cheng & Yi Lai & Min Li & Lei Yang & Peifeng Liu & Xiao-hua Chen & Min Huang & Haijun Yu & Huixiong Xu & Zhiai Xu, 2024. "A region-confined PROTAC nanoplatform for spatiotemporally tunable protein degradation and enhanced cancer therapy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    15. Zijuan Li & Yuyun Zhang & Ci-Hang Ding & Yan Chen & Haoyu Wang & Jinyu Zhang & Songbei Ying & Meiyue Wang & Rongzhi Zhang & Jinyi Liu & Yilin Xie & Tengfei Tang & Huishan Diao & Luhuan Ye & Yili Zhuan, 2023. "LHP1-mediated epigenetic buffering of subgenome diversity and defense responses confers genome plasticity and adaptability in allopolyploid wheat," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    16. Hui Yang & Qingqing Li & Xingxing Chen & Mingzhe Weng & Yakai Huang & Qiwen Chen & Xiaocen Liu & Haoyu Huang & Yanhuizhi Feng & Hanyu Zhou & Mengying Zhang & Weiya Pei & Xueqin Li & Qingsheng Fu & Lia, 2024. "Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    17. Yan, Kexun & Wang, Maoxiang & Hu, Fenglan & Xu, Meng, 2023. "Effect of cellular dedifferentiation on the growth of cell lineages," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 632(P1).
    18. Shiqian Ma & Daniel Johnson & Cody Ashby & Donghai Xiong & Carole L Cramer & Jason H Moore & Shuzhong Zhang & Xiuzhen Huang, 2015. "SPARCoC: A New Framework for Molecular Pattern Discovery and Cancer Gene Identification," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-19, March.
    19. Qiuchen Guo & Milos Spasic & Adam G. Maynard & Gregory J. Goreczny & Amanuel Bizuayehu & Jessica F. Olive & Peter Galen & Sandra S. McAllister, 2022. "Clonal barcoding with qPCR detection enables live cell functional analyses for cancer research," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Hoang Pham, 2022. "Mathematical Modeling the Time-Delay Interactions between Tumor Viruses and the Immune System with the Effects of Chemotherapy and Autoimmune Diseases," Mathematics, MDPI, vol. 10(5), pages 1-15, February.

    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:15:y:2024:i:1:d:10.1038_s41467-024-50987-6. 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.