GSE104559
HNRNPH1 is required for rhabdomyosarcoma cell growth and survival
Rhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer characterized by a muscle-like phenotype. Although the average 5-year survival rate is 65% for newly diagnosed RMS, the treatment options for metastatic disease are limited in efficacy, with the 5-year 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 3 cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1, growth of all cell lines was dramatically 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 striking reduction in 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 show that HNRNPH1 may be an important molecular target for the development of future RMS therapy. Overall design: Two individual siRNAs targeting HNRNPH1 were used to knockdown HNRNPH1 in RD, RH30, and RH41 cells. Both siRNAs were done in triplicate in all cell lines. Briefly, 20nM siRNA was transfected with RNAiMax in 6-well dishes (2?×?105 RD and RH30 or 2.4?×?105 RH41) for 12 hours, after which media was changed and cells collected 48 hours post transfection.