Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer
Stefano Cairo,Yipeng Wang,Aurélien de Reyniès,Karine Duroure,Jennifer Dahan,Marie-José Redon,Monique Fabre,Michael McClelland,Xin Wei Wang,Carlo M. Croce,Marie-Annick Buendia +10 more
TLDR
The data argue that Myc-driven reprogramming of miR expression patterns contributes to the aggressive phenotype of liver tumors originating from hepatic progenitor cells.Abstract:
Myc activation has been implicated in the pathogenesis of hepatoblastoma (HB), a rare embryonal neoplasm derived from liver progenitor cells. Here, microRNA (miR) expression profiling of 65 HBs evidenced differential patterns related to developmental stage and Myc activity. Undifferentiated aggressive HBs overexpressed the miR-371–3 cluster with concomitant down-regulation of the miR-100/let-7a-2/miR-125b-1 cluster, evoking an ES cell expression profile. ChIP and Myc inhibition assays in hepatoma cells demonstrated that both miR clusters are regulated by Myc in an opposite manner. We show that the two miR clusters exert antagonistic effects on cell proliferation and tumorigenicity. Moreover, their combined deregulation cooperated in modulating the hepatic tumor phenotype, implicating stem cell-like regulation of Myc-dependent miRs in poorly differentiated HBs. Importantly, a four-miR signature representative of these clusters efficiently stratified HB patients, and when applied to 241 hepatocellular carcinomas (HCCs), it identified invasive tumors with a poor prognosis. Our data argue that Myc-driven reprogramming of miR expression patterns contributes to the aggressive phenotype of liver tumors originating from hepatic progenitor cells.read more
Citations
More filters
Journal ArticleDOI
The microcosmos of cancer
TL;DR: The discovery of microRNAs almost two decades ago established a new paradigm of gene regulation, and during the past ten years these tiny non-coding RNAs have been linked to virtually all known physiological and pathological processes, including cancer.
Journal ArticleDOI
Cancer stem cells in the development of liver cancer
Taro Yamashita,Xin Wei Wang +1 more
TL;DR: An increased understanding of the molecular signaling events that regulate cellular hierarchy and stemness, and success in defining key CSC-specific genes, have opened up new avenues to accelerate the development of novel diagnostic and treatment strategies.
Journal ArticleDOI
MicroRNAs in Liver Disease
TL;DR: The role of microRNAs in liver physiology and pathophysiology is reviewed, focusing on viral hepatitis, liver fibrosis, and cancer.
Journal ArticleDOI
How does Lin28 let-7 control development and disease?
TL;DR: This review focuses on current understanding of the Lin28-mediated control of let-7 maturation and highlights the central role of Lin28 in stem cell biology, development, control of glucose metabolism, and dysregulation in human disease.
Journal ArticleDOI
Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium
Dolores Lopez-Terrada,Rita Alaggio,Maria T. De Dávila,Piotr Czauderna,Eiso Hiyama,Howard M. Katzenstein,Ivo Leuschner,Marcio H. Malogolowkin,Rebecka L. Meyers,Sarangarajan Ranganathan,Yukichi Tanaka,Gail E. Tomlinson,Monique Fabre,Arthur Zimmermann,Milton J. Finegold +14 more
TL;DR: This symposium represented the first collaborative step to develop a classification that may lead to a common treatment-stratification system incorporating tumor histopathology and work towards an International Pediatric Liver Tumors Consensus Classification.
References
More filters
Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal Article
MicroRNA signatures in human cancers
George A. Calin,Carlo M. Croce +1 more
TL;DR: The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery as discussed by the authors.
Journal ArticleDOI
A microRNA polycistron as a potential human oncogene
Lin He,J. Michael Thomson,Michael T. Hemann,Eva Hernando-Monge,David Mu,Summer G. Goodson,Scott Powers,Carlos Cordon-Cardo,Scott W. Lowe,Gregory J. Hannon,Scott M. Hammond +10 more
TL;DR: It is found that the levels of the primary or mature microRNAs derived from the mir-17–92 locus are often substantially increased in human B-cell lymphomas, and the cluster is implicate as a potential human oncogene.
Journal ArticleDOI
An embryonic stem cell–like gene expression signature in poorly differentiated aggressive human tumors
Ittai Ben-Porath,Matt Thomson,Vincent J. Carey,Ruping Ge,George W. Bell,Aviv Regev,Robert A. Weinberg +6 more
TL;DR: The results reveal a previously unknown link between genes associated with ES cell identity and the histopathological traits of tumors and support the possibility that these genes contribute to stem cell–like phenotypes shown by many tumors.
Journal ArticleDOI
Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer Model
Janaiah Kota,Raghu R. Chivukula,Kathryn A. O'Donnell,Erik A. Wentzel,Chrystal L. Montgomery,Hun-Way Hwang,Tsung Cheng Chang,Perumal Vivekanandan,Michael Torbenson,K. Reed Clark,K. Reed Clark,Jerry R. Mendell,Jerry R. Mendell,Joshua T. Mendell +13 more
TL;DR: It is demonstrated that hepatocellular carcinoma (HCC) cells exhibit reduced expression of miR-26a, a miRNA that is normally expressed at high levels in diverse tissues that may provide a general strategy for miRNA replacement therapies.
Related Papers (5)
MicroRNA expression profiles classify human cancers
Jun Lu,Gad Getz,Eric A. Miska,Eric A. Miska,Ezequiel Alvarez-Saavedra,Justin Lamb,David Peck,Alejandro Sweet-Cordero,Alejandro Sweet-Cordero,Benjamin L. Ebert,Benjamin L. Ebert,Raymond H. Mak,Raymond H. Mak,Adolfo A. Ferrando,James R. Downing,Tyler Jacks,H. Robert Horvitz,H. Robert Horvitz,Todd R. Golub,Todd R. Golub,Todd R. Golub +20 more