Shiraz University Press Molecular Biology Research Communications 2322-181X 13 1 2024 03 01 The importance of examining the Hardy-Weinberg Equilibrium in genetic association studies 1 2 7213 10.22099/mbrc.2023.48386.1872 EN Mostafa Saadat Department of Biology, School of Science, Shiraz University, Shiraz, Iran Journal Article 2023 09 18 No abstract https://mbrc.shirazu.ac.ir/article_7213_ff18ae672e9414004d425f7a8afea250.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 13 1 2024 03 01 Arginine to glutamine mutation in the substrate binding region impaired the isopentenyl activity of Mycobacterium tuberculosis MiaA 3 9 7214 10.22099/mbrc.2023.47247.1825 EN Smitha Soman School of Biotechnology, Gautam Buddha University, Gautam Budh Nagar, Greater Noida, Uttar Pradesh, India Siya Ram School of Biotechnology, Gautam Buddha University, Gautam Budh Nagar, Greater Noida, Uttar Pradesh, India School of Sciences, Indira Gandhi National Open University, Maidan Garhi, New Delhi, India Journal Article 2023 04 29 tRNAs act as adaptors during protein synthesis and are chemically modified post-transcriptionally for their structural stability as well as accuracy of the translation. Hypomodifications of tRNAs are known to cause various human diseases, including cancer. Studies in bacteria and yeasts showed that levels of tRNA modifications vary under different stress conditions, enabling the organism to modulate gene expression for survival. Isopentelylation of the base 37 (i6A37) in the anticodon stem-loop by tRNA isopentenyltransferase (MiaA) is well-conserved modification present in prokaryotes and eukaryotes. i6A37 modification increases both the speed and fidelity of translation. A homozygous p.Arg323Gln mutation in the tRNA binding region of tRNA isopentenyltransferase reduced i6A37 levels in humans, affecting mitochondrial translation and thereby causing neurodevelopmental disorder. In this study, we mutated the Arg residue at the conserved position to Gln in Mycobacterium tuberculosis (M. tb) MiaA and analyzed the i6A modification activity of the enzyme on its target tRNAs. We found that p.Arg274Gln mutant MiaA could not modify the target tRNAs, tRNALeuCAA, tRNAPheGAA, and tRNASerCGA from M. tb, confirming the role of Arg residue in tRNA binding.

https://mbrc.shirazu.ac.ir/article_7214_7c878d8ac3462cd7c84ce129e43cacfd.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 13 1 2024 03 01 Evaluation of Beclin1 and mTOR genes and p62 protein expression in breast tumor tissues of Iranian patients 11 19 7218 10.22099/mbrc.2023.47597.1837 EN Maryam Adelipour Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Mahshid Naghashpour Department of Nutrition, Shool of Medicine, Abadan University of Medical Science, Abadan, Iran Mohammad Reza Roshanazadeh Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Hadi Chenaneh Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Asma Mohammadi Department of Biochemistry, Shool of Medicine, Abadan University of Medical Science, Abadan, Iran Pegah Pourangi Department of Biochemistry, Shool of Medicine, Abadan University of Medical Science, Abadan, Iran Seyed Rouhollah Miri Department of surgical oncology, Cancer institute, Tehran University of Medical Science Atefeh Zahedi Asadabad School of Medical Sciences, Asadabad, Iran Mahmood Haghighatnezhad Department of Biochemistry, Shool of Medicine, Abadan University of Medical Science, Abadan, Iran Sahar Golabi Department of Physiology, Shool of Medicine, Abadan University of Medical Science, Abadan, Iran Journal Article 2023 06 08 Autophagy is a cellular process that plays a major role in the fate of tumor cells. Understanding the role of autophagy in cancer therapy is a major challenge, particularly for breast cancer as the sole top cause of mortality among women. In this study, we evaluated the gene expression of mTOR and Beclin1 and the levels of p62 protein, in breast tumors and compared them to a control condition. To explore the role of autophagy in breast cancer, we acquired tumor biopsies from 41 new cases of breast cancer patients. We extracted total RNA from each biopsy and used real-time PCR to quantify Beclin1 and mTOR-specific RNA expression. In addition, we evaluated the expression of the p62 protein in paraffin-embedded tumor tissue using the immunohistochemistry technique. The data revealed an upregulation of Beclin1 and a downregulation of mTOR in tumor tissues compared to the control condition. The correlation between p62 expression and Beclin1/mTOR showed a negative and positive correlation, respectively, confirming autophagy activation in the tumor tissues. However, there was no correlation between autophagy markers and tumor size, grade and stage. The findings revealed that autophagy activation was found in breast tumor tissues, suggesting that autophagy can be a target for breast cancer therapy.

https://mbrc.shirazu.ac.ir/article_7218_93826f2404274493d0194137ea92c2af.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 13 1 2024 03 01 MicroRNAs targeting CDKN2A gene as a potential prognostic marker in head and neck squamous cell carcinoma 21 27 7222 10.22099/mbrc.2023.48081.1853 EN Sivakumar Gopalakrishnan Clinical Genetics Lab, Centre for Cellular and Molecular Research, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Chennai, India Anitha Pandi Clinical Genetics Lab, Centre for Cellular and Molecular Research, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Chennai, India Paramasivam Arumugam Molecular Biology Lab, Centre for Cellular and Molecular Research, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Chennai, India Vijayashree Priyadharsini Jayaseelan Clinical Genetics Lab, Centre for Cellular and Molecular Research, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Chennai, India Journal Article 2023 08 13 Epigenetic factors are known to markedly influence the functions of a gene by modification of transcripts, via methylation or acetylation and degradation of mRNA transcripts. The CDKN2A encodes cyclin-dependent kinase inhibitor 2A, a tumour suppressor protein. Genetic and epigenetic alterations in this gene have been demonstrated in several cancer types. The non-coding RNAs with a special emphasis on microRNAs have long been explored for their potential role in the epigenetic modification of gene expression. The present study aims to identify the microRNAs targeting CDKN2A gene transcripts and demonstrate their prognostic significance in head and neck squamous cell carcinoma (HNSCC). Computational approaches were employed to identify the microRNAs targeting CDKN2A. The gene and protein expression profile of CDKN2A was analyzed using UALCAN. A significant upregulation of CDKN2A was observed in the primary tumour tissues (p=<10-12). Interestingly, the protein expression, although found to be statistically significant (p=0.0129) did not correlate well with the gene expression profile. The microRNAs targeting CDKN2A were further analyzed to identify the possible reason for the decrease in protein expression. Among the 44 microRNAs targeting CDKN2A gene transcripts, hsa-miR-3681-3p, hsa-miR-542-5p, hsa-miR-4519 were found to be upregulated and hsa-miR-134-5p was found to be downregulated with a significant association with survival status of HNSCC patients. The hsa-miR-542-5p was found to correlate well with the survival and hence can be considered as the key microRNA associated with HNSCC. However, further validation of this microRNA is warranted to confirm its role in the process of carcinogenesis.

https://mbrc.shirazu.ac.ir/article_7222_bea11d5fefb9ed95bd12de107294cba3.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 13 1 2024 03 01 In-silico structural analysis of Heterocephalus glaber amyloid beta: an anti-Alzheimer's peptide 29 42 7224 10.22099/mbrc.2023.48223.1862 EN Ali Javanmard Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran Maryam Azimzadeh-Irani Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran Ghazal Tafazzoli Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran Ayla Esmaeilzadeh Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran Mohammad Shirinpoor-Kharf Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran Seyed Mohammad Hasan Haghayeghi Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran Journal Article 2023 09 02 Heterocephalus glaber, known as the Naked mole-rat, has an extraordinary immunity to Alzheimer's disease. The pathological hallmark of Alzheimer’s disease is cerebral accumulations of plaques, consisting of self-aggregated amyloid beta peptides. Homo sapiens and H. glaber amyloid beta peptides are different in only one amino acid. Herein, computational structural analyses were carried out to determine whether plaque development in H. glaber is prevented by the replacement of His13 with Arg13 in the amyloid beta peptide. AlphaFold2 was used to predict the structure of the H. glaber amyloid beta peptide. HADDOCK and Hex were used to self-dock the peptides and dock ions on peptides, respectively. Illustrations were made by PyMol and ChimeraX. Using VMD, we calculated the radius of gyration. The phylogenetic analysis was conducted by Mega. The results showed an accurate structure with two alpha helices separated by a short coil for H. glaber. Self-docking of the two amyloid beta peptides demonstrated a globular conformation in the H. glaber dimer, implying the unlikeliness of amyloid beta peptides’ self-aggregation to form fibrillar structures. This conformational state resulted in lower electrostatic energy compared to H. sapiens, contributing to H. glaber’s lower tendency for fibril and, ultimately, plaque formation. Phylogenetic analysis confirmed that amyloid precursor protein is highly conserved in each taxon of rodentia and primata. This study provides insight into the connection between the structure of H. glaber amyloid beta and its plaque formation properties, showing that the Arg13 in H. glaber leads to fibril instability, and might prevent senile plaque accumulation.

https://mbrc.shirazu.ac.ir/article_7224_ee5dc98a67e5e505c429164c5186b40c.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 13 1 2024 03 01 Allele and genotype frequencies of β-lactoglobulin gene using PCR-RFLP in Algerian local cattle populations 43 49 7227 10.22099/mbrc.2023.47661.1841 EN Nadjet Boushaba Laboratory Genetics Molecular and Cellular, Department of Molecular Genetics Applied, Faculty of Nature and Life Sciences, University of Science and Technology of Oran "Mohamed Boudiaf ", B.P 1505 El M’Naouar, 31000 Oran, Algeria Nacera Tabet-Aoul Laboratory Genetics Molecular and Cellular, Department of Molecular Genetics Applied, Faculty of Nature and Life Sciences, University of Science and Technology of Oran "Mohamed Boudiaf ", B.P 1505 El M’Naouar, 31000 Oran, Algeria Journal Article 2023 06 17 Milk protein genetic polymorphisms are associated with economically important traits in dairy cattle. The objective of this study is to genotype a single nucleotide polymorphism (SNP) responsible for the amino acid changes in the beta-lactoglobulin (β-Lg) variants A and B on 85 unrelated DNA representing Algerian cattle populations: Chelifienne (28), Cheurfa (31) and Guelmoise (26). The method used is the PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). Genetic polymorphism was detected by digestion of PCR products amplified of exon II of β-Lg gene by with the endonuclease HaeIII enzyme. The results revealed that the amplified product was observed as 247 bp. Restriction digestion with HaeIII revealed three genotypes: AA, AB and BB. The genotypic frequencies of AA, AB and BB genotypes were 0.08, 0.41, 0.50; 0.08, 0.41, 0.50 and 0.01, 0.19, 0.56 in Chelifienne, Cheurfa and Guelmoise and respectively. Frequency of AA genotype was absent in Guelmoise population. Frequencies of A and B alleles were 0.29 and 0.71 in both Chelifienne and Cheurfa and 0.25 and 0.75 Guelmoise population. These results further confirm that Bos torus cattle are predominantly of β-Lactoglobulin B type. The Chi-square test at p-value < 0.05 results revealed that the Chelifienne and Cheurfa populations were in Hardy-Weinberg equilibrium and the results are not significant for the Guelmoise. This genetic information could be useful to estimate the effect of polymorphism on different milk production of Algerian bovine populations.

https://mbrc.shirazu.ac.ir/article_7227_625920802c3ccb75298c5aa534994e44.pdf