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Down-regulated and Commonly mutated ALPK1 in Lung and Colorectal Cancers
Hsien-Feng Liao1, Hsien-Hsiung Lee2,3, Ya-Sian Chang2,3
1The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, Taiwan.
Abstract:
The ALPK1 gene located in the 4q25 region encodes a newly explored protein kinase which could phosphorylate the amino acid of a domain full of α-helices. Recently, several studies have indicated that the expression of ALPK1 is related to inflammation and various diseases; therefore, the purpose of this investigation was to determine whether the expression of ALPK1 has an influence on tumorigenesis and to further scrutinize its gene polymorphism in order to better understand its clinical importance. In lung and colorectal cancer tissues, the ALPK1 RNA level of the normal part was higher than that of the tumor part using the RT-qPCR analysis. Moreover, differences in HRM melting curves could effectively separate the known mutation sites and be used to identify the two novel variants that might cause the bio-dysfunctions of ALPK1 found in silico predictions. Additionally, in both Lovo colorectal and A549 lung cancer cells with enhanced and depleted expression of ALPK1, the encoded ALPK1 could exert its activity on cell migration without interfering with cell viability. Taken together, these findings suggested that ALPK1 might play a vital role in cancer development and that the newly explored SNPs are found in a Taiwanese cohort.
Insights
The study found that the ALPK1 gene, linked to inflammation, plays a role in lung and colorectal cancer development. Researchers identified novel ALPK1 gene variants, suggesting potential clinical importance in cancer.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The ALPK1 gene encodes a protein kinase implicated in inflammation and various diseases.
- Previous research suggests a link between ALPK1 expression and disease pathogenesis.
Purpose of the Study:
- To investigate the influence of ALPK1 gene expression on tumorigenesis.
- To analyze ALPK1 gene polymorphism for clinical significance in cancer.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) to measure ALPK1 RNA levels in cancer tissues.
- High-resolution melting (HRM) curve analysis to identify gene variants.
- Functional assays in lung and colorectal cancer cell lines with altered ALPK1 expression.
Main Results:
- ALPK1 RNA levels were lower in lung and colorectal tumor tissues compared to normal tissues.
- HRM analysis identified two novel ALPK1 variants with potential bio-dysfunctions.
- ALPK1 expression modulated cell migration in cancer cells without affecting viability.
Conclusions:
- ALPK1 may play a significant role in cancer development.
- Novel ALPK1 single nucleotide polymorphisms (SNPs) were identified in a Taiwanese cohort, indicating potential clinical relevance.
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