HNRNPH1 is required for rhabdomyosarcoma cell growth and survival

Abstract

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.

Temporal Splicing Switches in Elements of the TNF-Pathway Identified by Computational Analysis of Transcriptome Data for Human Cell Lines

“…The HNRNPH1 gene is involved in splicing. It is overexpressed in many cancer types (e.g., rhabdomyosarcoma, esophageal squamous cell carcinoma and breast cancer) and is required for cancer growth and development [ 35 , 36 , 37 ]. Notably, the expression of the two isoforms of HNRNPH1 is different over time for the three investigated cell lines ( Figure S5 ).…”

“…Transcript variants of HNRNPH1 were shown to be differentially involved in tumorigenesis. Overall, positive expression of HNRNPH1 is associated with poor tumour differentiation degree [ 35 , 36 ]. The NME2 gene can act as a metastasis suppressor by altering telomere function and telomere length in lung cancer and fibroblasts [ 39 , 43 ].…”

Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

“…Cancer-related functions of PCBP2, TIA-1, HuR/ELAVL1, SERBP1, YTHDC2, YTHDF2 (Mapofthecell database) were described above. All experimentally defined partners of eEF1Bγ picked up by Cytoscape to build molecular networks, are linked to cancer as well [2,[125][126][127][128][129][130][131][132].…”

Genome-Wide Profiling of Alternative Splicing Signature Reveals Prognostic Predictor for Esophageal Carcinoma

“…Some of these SFs have been reported previously. For example, HNRNPH1, an RNA-binding protein highly expressed in many cancers, was found to alter the splicing of some oncogenes following knockdown, which then inhibits the tumor formation and growth in Rhabdomyosarcoma (Li et al, 2018). CLK1, a member of the CLKs family that phosphorylates SR proteins involved in splicing, was shown to promote the phosphorylation of SPF45 when overexpressed, which ultimately induces cell migration and invasion of ovarian cancer (Liu et al, 2013).…”