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Silencing effects of mutant RAS signalling on transcriptomes
Christine Sers1, Reinhold Schäfer2
1Laboratory of Molecular Tumor Pathology and systems Biology, Institute of Pathology, Charité Universitätstmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany; German Cancer Consortium, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany.
Advances in Biological Regulation
|December 13, 2022
Summary
RAS-mutated cancers alter gene expression, with suppressed factors potentially acting as tumor suppressors. This study investigates HREV107, a tumor suppressor, and its role in RAS-driven cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Mutated RAS genes drive many cancers, leading to significant alterations in cellular gene expression.
- While RAS-driven oncogenes upregulate factors like MYC, FOSL1, and HMGA2, the role of downregulated factors is less understood.
- These suppressed factors may function as tumor suppressors, counteracting cancer-driving mechanisms.
Purpose of the Study:
- To investigate the role of downregulated RAS-responsive factors in cancer.
- To focus on the tumor suppressor HREV107 (PLAAT3, PLA2G16, HRASLS3) and its mechanisms.
- To understand how RAS pathway modulation leads to HREV107 downregulation and loss of function.
Main Methods:
- Systematic gene expression studies in cellular models comparing pre-neoplastic and RAS-transformed cells.
- Analysis of RAS-responsive downregulated factors.
- Focus on the tumor suppressor HREV107 and its functional mechanisms.
Main Results:
- RAS activation alters a significant portion of the transcriptome, with roughly equal numbers of up- and down-regulated transcripts.
- Up-regulated factors like MYC, FOSL1, and HMGA2 are known drivers.
- Downregulated factors, including HREV107, are less studied but may act as tumor suppressors.
Conclusions:
- Downregulated RAS-responsive factors, such as HREV107, represent a critical area for cancer research.
- Epigenetic mechanisms modulated by the RAS pathway likely cause HREV107 downregulation, rather than inactivating mutations.
- Understanding these mechanisms is key to developing new anti-RAS cancer therapies.
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