miRNA Signatures Associate with Pathogenesis and Progression of Osteosarcoma
Kevin B. Jones,Zaidoun Salah,Sara Del Mare,Marco Galasso,Eugenio Gaudio,Gerard J. Nuovo,Francesca Lovat,Kimberly T. LeBlanc,Jeff Palatini,R. Lor Randall,Stefano Volinia,Gary S. Stein,Carlo M. Croce,Jane B. Lian,Rami I. Aqeilan +14 more
TLDR
A miRNA signature associated with pathogenesis of osteosarcoma as well as critical pre-treatment biomarkers of metastasis and responsiveness to therapy is established.Abstract:
Osteosarcoma remains a leading cause of cancer death in adolescents. Treatment paradigms and survival rates have not improved in two decades. Driving the lack of therapeutic inroads, the molecular etiology of osteosarcoma remains elusive. MicroRNAs (miRNAs) have demonstrated far-reaching effects on the cellular biology of development and cancer. Their role in osteosarcomagenesis remains largely unexplored. Here we identify for the first time an miRNA signature reflecting the pathogenesis of osteosarcoma from surgically procured samples from human patients. The signature includes high expression of miR-181a,miR-181b, and miR-181c as well as reduced expression of miR-16, miR-29b, and miR-142-5p. We also demonstrate that miR-181b and miR-29b exhibit restricted expression to distinct cell populations in the tumor tissue. Further, higher expression of miR-27a and miR-181c* in pre-treatment biopsy samples characterized patients who developed clinical metastatic disease. In addition, higher expression of miR-451 and miR-15b in pre-treatment samples correlated with subsequent positive response to chemotherapy. In vitro and in vivo functional validation in osteosarcoma cell lines confirmed the tumor suppressive role of miR-16 and the pro-metastatic role of miR-27a. Furthermore, predicted target genes for miR-16 and miR-27a were confirmed as down-regulated by real-time PCR. Affymetrix array profiling of cDNAs from the osteosarcoma specimens and controls were interrogated according to predicted targets of miR-16, miR142-5p, miR-29b, miR-181a/b, and miR-27a. This analysis revealed positive and negative correlations highlighting pathways of known importance to osteosarcoma, as well as novel genes. Thus, our findings establish a miRNA signature associated with pathogenesis of osteosarcoma as well as critical pre-treatment biomarkers of metastasis and responsiveness to therapy.read more
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The Pivotal Regulatory Landscape of RNA Modifications
Sheng Li,Christopher E. Mason +1 more
TL;DR: Both labile and permanent modifications, from simple methylation to complex transcript alteration (RNA editing and intron retention) are examined; the models for their processing are detailed; and remaining questions in the field of the epitranscriptome are highlighted.
Journal ArticleDOI
Modulation of the Osteosarcoma Expression Phenotype by MicroRNAs
Heidi M. Namløs,Leonardo A. Meza-Zepeda,Leonardo A. Meza-Zepeda,Tale Barøy,Ingrid H.G. Østensen,Stine H. Kresse,Marieke L. Kuijjer,Massimo Serra,Horst Bürger,Anne-Marie Cleton-Jansen,Ola Myklebost,Ola Myklebost +11 more
TL;DR: This study provides an integrated analysis of miRNA and mRNA in osteosarcoma, and gives new insight into the complex genetic mechanisms of osteosARcoma development and progression, as well as identifying 177 miRNAs that were differentially expressed in osteOSarcomA cell lines relative to normal bone.
Journal ArticleDOI
New Molecular Insights Into Osteosarcoma Targeted Therapy
Jilong Yang,Wei Zhang +1 more
TL;DR: These translational studies in osteosarcoma have identified new molecular targets for osteosARcoma that are involved in tumor proliferation and apoptosis and microRNAs such as miR-215 are also therapeutic targets.
Journal ArticleDOI
The MicroRNA miR-181 Is a Critical Cellular Metabolic Rheostat Essential for NKT Cell Ontogenesis and Lymphocyte Development and Homeostasis
Jorge Henao-Mejia,Adam Williams,Loyal A. Goff,Loyal A. Goff,Matthew M. Staron,Paula Licona-Limón,Susan M. Kaech,Susan M. Kaech,Maki Nakayama,John L. Rinn,John L. Rinn,Richard A. Flavell,Richard A. Flavell +12 more
TL;DR: It is reported that miR-181 is a nonredundant determinant of cellular metabolism and is essential for supporting the biosynthetic demands of early NKT cell development and establishes this family of miRNAs as central regulators of PI3K signaling and global metabolic fitness during development and homeostasis.
Journal ArticleDOI
Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity.
Weijia Sun,Chenyang Zhao,Yuheng Li,Liang Wang,Guangjun Nie,Jiang Peng,Aiyuan Wang,Pengfei Zhang,Weiming Tian,Qi Li,Jinping Song,Cheng Wang,Xiaolong Xu,Yanhua Tian,Dingsheng Zhao,Zi Xu,Guohui Zhong,Bingxing Han,Shukuan Ling,Yan Zhong Chang,Yingxian Li +20 more
TL;DR: It is reported that osteoclasts secrete microRNA-enriched exosomes, by which miR-214 is transferred into osteoblasts to inhibit their function, suggesting that exosome-mediated transfer of microRNA plays an important role in the regulation of osteoblast activity.
References
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Book ChapterDOI
The Epidemiology of Osteosarcoma
Giulia Ottaviani,Norman Jaffe +1 more
TL;DR: The overall 5-year survival rate for osteosarcoma is 68%, without significant gender difference, and the age of the patient is correlated with the survival, with the poorest survival among older patients.