Investigating Nucleotide Changes of LMO1 Gene as a Positive Regulator of Transcription in Patients with Glioblastoma Brain Tumors

Document Type : Research Paper

Authors

1 Master's student in Genetics, Department of Biology, Yazd University, Yazd, Iran

2 Associate Professor of Molecular Genetics, Department of Biology, Yazd University, Yazd, Iran, (corresponding author)

3 Associate Professor of Molecular Genetics, Department of Biology, Yazd University, Yazd, Iran

4 Neurology specialist, Department of Neurosurgery, Faculty of Medicine, Shahid Sadougi University of Medical Sciences, Yazd, Iran

Abstract

Introduction
Glioblastoma is one of the most malignant brain tumors, which is also known as primary neuroepithelial tumors. Glioblastoma malignant tumors include 20-40% of brain tumors. The LMO1 gene is located at position 11P15.4 and is introduced as an oncogene in some cancers. This study was conducted for the first time in Iran to identify and investigate the relationship between LMO1 gene mutations and glioblastoma.
method
In this research, the Touchdown PCR technique and DNA sequencing method were used in 35 blood samples of people with glioblastoma multiforme and 40 control samples. Bioinformatics analyses were also performed to investigate the pathogenic effect of nucleotide changes in this gene.
Results
In this study, four point mutations were identified, of which two of the new mutations were misense and led to amino acid changes in one of the important domains of the protein (p.M135K and p.N148H), which indicates their potential pathogenicity. Our results of bioinformatics databases predicted that both of these mutations affect protein function, such that they can disrupt this domain and impair its function. Also, a nucleotide change was observed in the 3'UTR region of this gene (c.*74A>G), which is located at the binding site of two regulatory miRNAs and is expected to disrupt the binding of these miRNAs to the target sequence.
Conclusion
These findings predict that any mutations in the LIM-sensitive domains in the LMO1 gene are significantly related to the pathogenesis of glioblastoma and most likely have a significant impact on the function of this transcriptional cofactor.

Keywords

Main Subjects

References

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Medical Journal of Mashhad university of Medical Sciences
Volume 67, Issue 4
May and June 2024
Pages 1289-1302

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