Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL)

Parastoo Hosseini; Abbas Rahimi Foroushani; Arezoo Marjani; Mahnaz Tavakoli; Abdollah Amiri; Amin Hosseini; Atefeh Bahavar; Sayed-Hamidreza Mozhgani; Mehdi Norouzi

doi:10.18502/ijm.v15i3.12910

Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL)

Iran J Microbiol. 2023 Jun;15(3):475-481. doi: 10.18502/ijm.v15i3.12910.

Authors

Parastoo Hosseini¹, Abbas Rahimi Foroushani², Arezoo Marjani¹, Mahnaz Tavakoli³, Abdollah Amiri⁴, Amin Hosseini⁵, Atefeh Bahavar⁶, Sayed-Hamidreza Mozhgani⁷, Mehdi Norouzi¹

Affiliations

¹ Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
² Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
³ Department of Medical Microbiology, School of Medical Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
⁵ Department of Computer, Faculty of Engineering, Raja University, Qazvin, Iran.
⁶ Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
⁷ Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.

Abstract

Background and objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals.

Materials and methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software.

Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database.

Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.

Keywords: Adult T-cell leukemia/lymphoma; HTLV-I-associated myelopathy; Keywords: Human T-lymphotropic virus type 1; MAP kinase/ERK kinase; Mitogen-activated protein kinase kinase 1; Tropical spastic paraparesis.