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Updated: Aug 15, 2026
Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
The Fem1a gene is downregulated in Rhabdomyosarcoma
Tereza Ventura-Holman1, Heidi Hahn, Jose S Subauste
1GV (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS 39216, USA.
Abstract:
Rhabdomyosarcoma (RMS) is the most common soft tissue neoplasm of children, and those metastatic at presentation have a poor prognosis. RMS development is related to defective skeletal muscle differentiation, involving a variety of cell signaling and transcriptional control pathways, including aberrant hedgehog signaling. Here we evaluate Fem1a, a gene highly expressed in skeletal muscle, as a candidate for involvement in RMS. Fem1a is a homolog of fem-1, which controls cell fate decisions in the sex determination pathway of Caenorhabditis elegans, a pathway with homology to mammalian hedgehog signaling. We show that Fem1a expression is activated during myocyte differentiation of C2C12 myoblasts, and this expression is largely confined to the terminally differentiating pool, not to the satellite-cell-like quiescent reserve cell pool. We find that the human homolog, FEM1A, is downregulated in all of 8 different human RMS cell lines, including those derived from embryonal and alveolar RMS. Using mouse genetic models of RMS development, we further show that Fem1a is consistently downregulated in primary RMS from Ptch1+/- mice, from p53-/- mice, from p53+/-; Ptch1+/- mice, and from HGF/SF-Ink4a/Arf-/- mice. Therefore, Fem1a downregulation may be involved in, and/or a marker of, an early cell fate defect fundamental to RMS pathogenesis.
Insights
Downregulation of the Fem1a gene may indicate early cell defects in pediatric rhabdomyosarcoma (RMS). This finding could serve as a marker for this aggressive childhood cancer.
Area of Science:
- Molecular Biology
- Developmental Biology
- Oncology
Background:
- Rhabdomyosarcoma (RMS) is a common pediatric soft tissue cancer with poor outcomes for metastatic cases.
- RMS pathogenesis involves defective skeletal muscle differentiation and aberrant cell signaling, including hedgehog pathways.
- Fem1a, a gene highly expressed in skeletal muscle, is investigated due to its homology to a key gene in Caenorhabditis elegans' sex determination pathway, which shares similarities with mammalian hedgehog signaling.
Purpose of the Study:
- To investigate the role of Fem1a in rhabdomyosarcoma (RMS) development.
- To determine if Fem1a expression is altered during myocyte differentiation and in RMS.
- To assess Fem1a as a potential marker for early cell fate defects in RMS.
Main Methods:
- Examined Fem1a gene expression during C2C12 myoblast differentiation.
- Analyzed FEM1A gene expression in human RMS cell lines.
- Investigated Fem1a expression in primary RMS tissues from various genetically engineered mouse models.
Main Results:
- Fem1a expression is activated during terminal myocyte differentiation in C2C12 cells.
- Human FEM1A is downregulated across multiple RMS cell lines (embryonal and alveolar subtypes).
- Fem1a is consistently downregulated in primary RMS from diverse mouse models, including those with Ptch1 and p53 mutations.
Conclusions:
- Fem1a downregulation appears to be associated with rhabdomyosarcoma.
- This downregulation may signify an early cell fate defect crucial to RMS pathogenesis.
- Fem1a could serve as a potential biomarker for rhabdomyosarcoma.
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