Research on RPL17-C18orf32
1. Target Summary:
RPL17-C18orf32 is a read-through transcript resulting from the fusion of the ribosomal protein L17 (RPL17) and the uncharacterized gene C18orf32. This gene is implicated in various diseases, including colorectal cancer and neurodevelopmental disorders. RPL17 is known for its role in ribosomal function and protein synthesis, while C18orf32 has been associated with glycosylphosphatidylinositol (GPI) biosynthesis defects, leading to neurological abnormalities.
2. Mechanism:
RPL17 is a component of the 60S ribosomal subunit, playing a crucial role in protein synthesis. It has been shown to influence cell proliferation and stemness in colorectal cancer through the ERK and NEK2/beta-catenin signaling pathways (Ko et al., 2022, PMID: 35711835). The RPL17-C18orf32 read-through transcript may have unique functions that contribute to tumorigenesis, as its expression is significantly upregulated in various cancers, including gastric cancer (Choi et al., 2016, PMID: 27833855). C18orf32, on the other hand, is involved in GPI anchor biosynthesis, which is essential for anchoring proteins to the cell surface. Defects in this process can lead to a range of phenotypes, particularly neurological disorders (Salian et al., 2022, PMID: 35107634).
3. Approved Drugs:
Currently, there are no specific approved drugs targeting the RPL17-C18orf32 read-through transcript. However, therapies targeting the pathways associated with RPL17, such as ERK and NEK2 inhibitors, may indirectly affect the outcomes related to RPL17-C18orf32.
4. Hypotheses:
- Tumorigenesis Hypothesis: RPL17 may contribute to tumorigenesis through its role in ribosomal function and signaling pathways, particularly in colorectal cancer.
- Neurodevelopmental Disorder Hypothesis: C18orf32 is critical for neurodevelopment, and its dysfunction may lead to developmental disorders characterized by hypotonia and contractures.
- Read-Through Transcript Hypothesis: The RPL17-C18orf32 read-through transcript may have unique regulatory functions that influence cellular processes in cancer and neurodevelopment.
5. Validation:
The association of RPL17 with colorectal cancer is supported by studies showing its upregulation in tumor tissues and its role in promoting cell proliferation (Ko et al., 2022, PMID: 35711835). C18orf32's link to neurodevelopmental disorders is validated by the identification of loss-of-function variants in affected individuals (Salian et al., 2022, PMID: 35107634). The expression of the RPL17-C18orf32 read-through transcript has been confirmed in gastric cancer tissues, indicating its potential role in tumor biology (Choi et al., 2016, PMID: 27833855).
6. Clinical Trials:
As of now, there are no specific clinical trials listed for RPL17-C18orf32. However, ongoing research into the individual components (RPL17 and C18orf32) may provide insights into potential therapeutic strategies.
7. Involved Pathways:
- ERK Signaling Pathway: Involved in cell proliferation and survival, particularly in cancer.
- NEK2/beta-catenin Pathway: Plays a role in mitotic progression and stemness maintenance in colorectal cancer.
- GPI Biosynthesis Pathway: Critical for anchoring proteins to the cell surface, affecting cellular signaling and function.
8. Associated Genes:
- RPL17: Ribosomal protein involved in protein synthesis and cell growth.
- C18orf32: Uncharacterized gene associated with GPI biosynthesis and neurodevelopmental disorders.
9. Target Expression:
RPL17-C18orf32 is expressed in various tissues, with significant upregulation observed in cancerous tissues, particularly in colorectal and gastric cancers (Choi et al., 2016, PMID: 27833855).
10. Additional Context:
The RPL17-C18orf32 read-through transcript represents a novel area of research, with implications for understanding the molecular mechanisms underlying cancer and neurodevelopmental disorders. Further studies are needed to elucidate its specific functions and potential as a therapeutic target.
11. References:
- Ko, M. J., Seo, Y. R., & Seo, D. (2022). RPL17 Promotes Colorectal Cancer Proliferation and Stemness through ERK and NEK2/beta-catenin Signaling Pathways. Journal of Cancer, PMID: 35711835.
- Salian, S., Guo, X. Y., & Murakami, Y. (2022). C18orf32 loss-of-function is associated with a neurodevelopmental disorder with hypotonia and contractures. Human Genetics, PMID: 35107634.
- Choi, E. S., Lee, H., & Lee, C. H. (2016). Overexpression of KLHL23 protein from read-through transcription of PHOSPHO2-KLHL23 in gastric cancer increases cell proliferation. FEBS Open Bio, PMID: 27833855.