TY - JOUR
T1 - HNRNPH1 is required for rhabdomyosarcoma cell growth and survival
AU - Li, Yanfeng
AU - Bakke, Jesse
AU - Finkelstein, David
AU - Zeng, Hu
AU - Wu, Jing
AU - Chen, Taosheng
N1 - Funding Information:
We thank the Hartwell Center (St. Jude Children’s Research Hospital) for analyzing the RNA-seq data; Nisha Badders (St. Jude Department of Scientific Editing) for editing the manuscript; Didier Trono (Global Health Institute at École Polytechnique Fédérale de Lausanne) for the psPAX2 and pMD2.G constructs; Dmitri Wiederschain (Novartis Institutes for Biomedical Research, Inc) for the Tet-pLKO-puro plasmid; Dr. Michael A. Dyer, Dr. Elizabeth Stewart, and the Childhood Solid Tumor Network (CSTN) for the PDX samples; Christopher Brewer and Dr. Yueming Wang for technical assistance; and other members of the Chen research laboratory for valuable discussions regarding this manuscript. This work was supported, in part, by ALSAC and the National Institutes of Health [grant numbers RO1-GM110034, R35-GM118041, and P30-CA21765].
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Rhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer characterized by a muscle-like phenotype. Although the average 5-y survival rate is 65% for newly diagnosed RMS, the treatment options for metastatic disease are limited in efficacy, with the 5-y survival rate plummeting to 30%. Heterogenous nuclear ribonucleoprotein H1 (HNRNPH1) is an RNA-binding protein that is highly expressed in many cancers, including RMS. To determine the role HNRNPH1 plays in RMS tumorigenesis, we investigated its expression and effect on growth in three cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1, growth of all cell lines was reduced, most likely through a combination of apoptosis and cell cycle arrest. We then recapitulated this finding by performing in vivo xenograft studies, in which knockdown of HNRNPH1 resulted in a reduction of tumor formation and growth. We used RNA sequencing to identify changes in gene expression after HNRNPH1 knockdown and found altered splicing of some oncogenes. Our data contribute to understanding the role of HNRNPH1 in RMS development.
AB - Rhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer characterized by a muscle-like phenotype. Although the average 5-y survival rate is 65% for newly diagnosed RMS, the treatment options for metastatic disease are limited in efficacy, with the 5-y survival rate plummeting to 30%. Heterogenous nuclear ribonucleoprotein H1 (HNRNPH1) is an RNA-binding protein that is highly expressed in many cancers, including RMS. To determine the role HNRNPH1 plays in RMS tumorigenesis, we investigated its expression and effect on growth in three cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1, growth of all cell lines was reduced, most likely through a combination of apoptosis and cell cycle arrest. We then recapitulated this finding by performing in vivo xenograft studies, in which knockdown of HNRNPH1 resulted in a reduction of tumor formation and growth. We used RNA sequencing to identify changes in gene expression after HNRNPH1 knockdown and found altered splicing of some oncogenes. Our data contribute to understanding the role of HNRNPH1 in RMS development.
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U2 - 10.1038/s41389-017-0024-4
DO - 10.1038/s41389-017-0024-4
M3 - Article
AN - SCOPUS:85040994933
SN - 2157-9024
VL - 7
JO - Oncogenesis
JF - Oncogenesis
IS - 1
M1 - 0024
ER -