Journal ArticleDOI
Impaired microRNA processing enhances cellular transformation and tumorigenesis.
Madhu S. Kumar,Jun Lu,Jun Lu,Kim L. Mercer,Todd R. Golub,Todd R. Golub,Todd R. Golub,Tyler Jacks +7 more
Reads0
Chats0
TLDR
It is shown that global repression of miRNA maturation promotes cellular transformation and tumorigenesis, and abrogation of global miRNA processing promotes tumorigenisation.Abstract:
MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate the expression of target mRNA transcripts. Many of these target mRNA transcripts are involved in proliferation, differentiation and apoptosis, processes commonly altered during tumorigenesis. Recent work has shown a global decrease of mature miRNA expression in human cancers. However, it is unclear whether this global repression of miRNAs reflects the undifferentiated state of tumors or causally contributes to the transformed phenotype. Here we show that global repression of miRNA maturation promotes cellular transformation and tumorigenesis. Cancer cells expressing short hairpin RNAs (shRNAs) targeting three different components of the miRNA processing machinery showed a substantial decrease in steady-state miRNA levels and a more pronounced transformed phenotype. In animals, miRNA processing-impaired cells formed tumors with accelerated kinetics. These tumors were more invasive than control tumors, suggesting that global miRNA loss enhances tumorigenesis. Furthermore, conditional deletion of Dicer1 enhanced tumor development in a K-Ras-induced mouse model of lung cancer. Overall, these studies indicate that abrogation of global miRNA processing promotes tumorigenesis.read more
Citations
More filters
Journal ArticleDOI
Non-coding RNAs in human disease
TL;DR: Dysregulation of these ncRNAs is being found to have relevance not only to tumorigenesis, but also to neurological, cardiovascular, developmental and other diseases, and there is great interest in therapeutic strategies to counteract these perturbations.
Journal ArticleDOI
Many roads to maturity: microRNA biogenesis pathways and their regulation
TL;DR: Recent advances in knowledge of the microRNA biosynthesis pathways are reviewed and their impact on post-transcriptional microRNA regulation during tumour development is discussed.
Journal ArticleDOI
MicroRNAs in cancer.
TL;DR: In this paper, the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies are discussed.
Journal ArticleDOI
Endogenous human microRNAs that suppress breast cancer metastasis
Sohail F. Tavazoie,Claudio Alarcón,Thordur Oskarsson,David Padua,Qiongqing Wang,Paula D. Bos,William L. Gerald,Joan Massagué +7 more
TL;DR: It is shown that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer cells in vivo, and miR-126 restoration reduces overall tumour growth and proliferation, whereasmiR-335 inhibits metastatic cell invasion.
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.
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 ArticleDOI
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
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
Journal ArticleDOI
A microRNA expression signature of human solid tumors defines cancer gene targets
Stefano Volinia,George A. Calin,Chang Gong Liu,Stefan Ambs,Amelia Cimmino,Fabio Petrocca,Rosa Visone,Marilena V. Iorio,Claudia Roldo,Manuela Ferracin,Robyn L. Prueitt,Nozumu Yanaihara,Giovanni Lanza,Aldo Scarpa,Andrea Vecchione,Massimo Negrini,Curtis C. Harris,Carlo M. Croce +17 more
TL;DR: The results indicate that miRNAs are extensively involved in cancer pathogenesis of solid tumors and support their function as either dominant or recessive cancer genes.
Journal ArticleDOI
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
TL;DR: It is shown that siRNA expression mediated by this vector causes efficient and specific down-regulation of gene expression, resulting in functional inactivation of the targeted genes.
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.
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