Integrative Analysis of the AMPK subunits in Colorectal Adeno Carcinoma
Beena T B1, Jesil Mathew A1, Harikumar K B2
1Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Science, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India.
Background:
The 5-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an emerging cancer treatment and therapeutic target. Due to the enzyme's complexity and dual nature, it is a confounding target in the treatment strategy. The study aimed to conduct an integrative analysis of the seven subunits and twelve isoforms of AMPK, which is not reported so far in colorectal adenocarcinoma patients.
Methodology:
The web-based tools UALCAN, Timer 2.0, KM Plotter, cBioPortal, COSMIC, and STRING were used to investigate the differential expression of AMPK subunits, protein-level Expression, promoter methylation status, survival analyses, Enrichment analysis, and protein-protein interaction.
Results:
The mRNA expression of AMPK subunits are upregulated in Colorectal Adeno Carcinoma (COAD), while the protein expression is comparatively reduced in colon tumors. The protein-level expression of α2 and β2 is decreased significantly in COAD patients. The γ3 subunit in colon tumor is hypermethylated. The study also reports that Liver Kinase B1 mutation in 7% of CRC patients, which might be the reason for downregulation of the gene and the protein expression of AMPK subunits in COAD.
Conclusion:
The Overall analysis of the subunits affirms that AMPK expression is beneficial in cancer.
Insights
5-adenosine monophosphate (AMP)-activated protein kinase (AMPK) expression is beneficial in cancer. This study analyzed AMPK subunits in colorectal adenocarcinoma, finding complex expression patterns that warrant further investigation for therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- 5-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a promising therapeutic target for cancer treatment.
- The complex and dual nature of AMPK presents challenges for effective therapeutic strategies.
- Investigating the seven subunits and twelve isoforms of AMPK in colorectal adenocarcinoma is crucial for understanding its role.
Purpose of the Study:
- To conduct an integrative analysis of AMPK subunits and isoforms in colorectal adenocarcinoma patients.
- To explore the differential expression, methylation status, and protein-protein interactions of AMPK in COAD.
- To determine the clinical significance of AMPK expression in colorectal cancer.
Main Methods:
- Utilized web-based bioinformatics tools: UALCAN, Timer 2.0, KM Plotter, cBioPortal, COSMIC, and STRING.
- Analyzed differential mRNA and protein expression of AMPK subunits.
- Investigated promoter methylation, survival data, and protein-protein interactions.
Main Results:
- AMPK subunit mRNA expression is upregulated in Colorectal Adeno Carcinoma (COAD), but protein expression is reduced.
- Specific subunits, α2 and β2, showed significantly decreased protein levels in COAD patients.
- The γ3 subunit exhibited hypermethylation in colon tumors, and Liver Kinase B1 mutations may contribute to AMPK downregulation.
Conclusions:
- AMPK expression is generally beneficial in cancer, despite complex regulatory mechanisms observed in COAD.
- The findings highlight the intricate role of AMPK in colorectal adenocarcinoma.
- Further research into AMPK's subunits and isoforms could lead to novel cancer treatment strategies.
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