Shiraz University Press Molecular Biology Research Communications 2322-181X 14 3 2025 09 01 The importance of TP53 status in cancer therapy: The example of chronic lymphocytic leukemia 179 198 7935 10.22099/mbrc.2025.51477.2054 EN Regina Mirgayazova Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia Raniya Khadiullina Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia Elvina Gilyazova Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia Damir Davletshin Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia Irina Ganeeva Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia Ekaterina Zmievskaya Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia Vitaly Chasov Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia Aygul Valiullina Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia Emil Bulatov Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia Journal Article 2024 10 21 The TP53 gene encodes the tumor suppressor protein p53, which plays a critical role in genomic stability and cell cycle regulation. TP53 mutations are prevalent in approximately half of all human malignancies and are associated with poor clinical outcomes, including increased genomic instability, chemoresistance, and reduced survival rates. However, the prognostic and predictive value of TP53 status remains inconsistent across cancer types. Chronic lymphocytic leukemia (CLL) stands out as a disease where TP53 alterations have a well-established clinical significance, influencing treatment decisions and patient prognosis. In CLL, TP53 mutations and 17p deletions are strongly correlated with advanced disease stages, resistance to chemo-immunotherapy, and poor overall survival. The European Research Initiative for CLL (ERIC) has recognized TP53 status as a crucial prognostic biomarker, advocating for its routine assessment in clinical practice. Given the limitations of traditional therapies in TP53-mutated CLL, novel targeted therapies, including BCL2 and BTK inhibitors, as well as CAR-T cell therapy, are being explored to improve patient outcomes. This review provides an in-depth analysis of the evolving role of TP53 status in CLL, with a particular focus on emerging therapeutic strategies, including CAR-T cell therapy, and their potential to overcome TP53-driven treatment resistance.

https://mbrc.shirazu.ac.ir/article_7935_77ad2f9f8ec878a7783fd32a36cf98c3.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 14 3 2025 09 01 Breast cancer susceptibility is associated with Cyclin D1 single nucleotide polymorphisms in Iran: A case-control study 199 202 7936 10.22099/mbrc.2025.51763.2065 EN Sadaf Soleimani Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran Soheila Talesh Sasani Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran Zivar Salehi Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran Fereshteh Fakour Medicine School, Guilan Medical University, Rasht, Iran Journal Article 2024 11 25 Breast cancer (BC) is the main cause of cancer-related death in women worldwide. We evaluated the association between the key CCND1 gene variant; rs9344 (G>A); and BC risk in Iran. In this case-control study, blood samples were obtained from 58 patients and 66 healthy controls. Genotyping was conducted by tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR). Statistical analysis was performed by MedCalc software. Our results showed that the polymorphism rs9344 has an association with BC risk in the Iranian population. Based on the codominant and recessive models, carriers of the AA genotype are nearly 3.5 times more susceptible to BC than other individuals, and the AA genotype of CCND1 A870G may be a significant factor for breast cancer. Further studies are needed to clarify the roles of CCND1 polymorphism, rs9344, in breast cancer.

https://mbrc.shirazu.ac.ir/article_7936_1ffc1db5135fbafa47e29fe0ac0ad545.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 14 3 2025 09 01 Gene co-expression network analysis reveals relationship between leukocyte fraction and genomic instability in dedifferentiated liposarcoma 203 218 7939 10.22099/mbrc.2025.51329.2050 EN Mohammad Darzi Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Medical Informatics Research Group, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Mahdieh Shokrollahi-Barough ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran Elahe Nazari Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Keivan Majidzadeh-A Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Rezvan Esmaeili Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Journal Article 2024 10 03 Dedifferentiated Liposarcoma (DDLPS) is one of the common subtypes of liposarcoma that is considered a highly malignant category. This study aims to investigate DDLPS through a system biology approach. The gene expression profiles and clinical traits of the DDLPS were acquired from The Cancer Genome Atlas (TCGA). The identification of co-expressed modules was conducted using the weighted gene co-expression network analysis. The immune cell-related gene function was studied by a web-based tool, TIMER, and, the survival analysis was performed at both the module and single-gene levels through Cox Regression analysis. Gene enrichment analysis was also conducted using the DAVID tool. One of the nine co-expressed DDLPS modules was significantly correlated with leukocyte fraction, hyper/hypo methylation, tumor purity, and chromosome instability (CIN). Based on the biological processes used to classify genes, the hub genes in a particular module play important roles in DNA repair, microtubule organizing clusters, mitotic checkpoint dysregulation, and cell proliferation signaling pathways. After screening the genes based on intra-module connectivity, module membership, and gene significance RAD54L was selected as one of the important hub genes. RAD54L showed poor prognosis to the overall survival (OS) analysis (HR=1.6, 95% CI=1.1–2.4, p=0.02). No co-expressed modules had relationship with OS. Through DDLPS traits, CIN and hyper/hypo methylation had significant negative relationship with OS. Our achievement confirmed the inverse association between tumor purity for DDLPS gene profiles and leukocyte fraction and negative leukocyte fraction (LF) gene significance in some genes was justified according to the sub-population analyses of immune cells in TIMER.

https://mbrc.shirazu.ac.ir/article_7939_0cc6ec76f71a7c86cf6b01ea1b51403e.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 14 3 2025 09 01 Comprehensive computational analysis of deleterious nsSNPs in PTEN gene for structural and functional insights 219 236 7976 10.22099/mbrc.2025.52148.2092 EN Divyanshi Sharma Department of Bioinformatics, Goswami Ganesh Dutta Sanatan Dharma College, Sector 32C, 160030, Chandigarh, India Harasees Singh Department of Bioinformatics, Goswami Ganesh Dutta Sanatan Dharma College, Sector 32C, 160030, Chandigarh, India Aryan Arya Department of Bioinformatics, Goswami Ganesh Dutta Sanatan Dharma College, Sector 32C, 160030, Chandigarh, India Himanshi Choudhary Department of Bioinformatics, Goswami Ganesh Dutta Sanatan Dharma College, Sector 32C, 160030, Chandigarh, India Pragya Guleria Department of Bioinformatics, Goswami Ganesh Dutta Sanatan Dharma College, Sector 32C, 160030, Chandigarh, India Sandeep Saini Department of Bioinformatics, Goswami Ganesh Dutta Sanatan Dharma College, Sector 32C, 160030, Chandigarh, India Department of Biophysics, Panjab University, Sector 25, 160014, Chandigarh, India Chander Jyoti Thakur Department of Bioinformatics, Goswami Ganesh Dutta Sanatan Dharma College, Sector 32C, 160030, Chandigarh, India Journal Article 2025 01 28 Single nucleotide polymorphisms (SNPs) are pivotal in understanding the genetic basis of complex disorders. Among them, nonsynonymous SNPs (nsSNPs) that alter amino acid sequences can significantly impact protein structure and function. This study focuses on analyzing deleterious nsSNPs in the tumor suppressor gene PTEN (Phosphatase and TENsin Homolog), which plays a central role in regulating the PI3K/Akt signaling pathway and tumorigenesis. Out of 43,855 SNPs in PTEN, 17 deleterious nsSNPs were identified using six computational tools. Protein stability analysis revealed that 15 variants reduce stability, potentially leading to functional impairment. Structural evaluations using HOPE and ConSurf classified mutations into buried structural residues disrupting protein integrity and exposed functional residues affecting molecular interactions. STRING database analysis highlighted PTEN as a central node in an intricate protein network, with deleterious mutations impairing critical interactions with partners such as PIK3CA, AKT1, and TP53. Secondary structure analysis revealed distinct structural deviations, particularly for G129E, which exhibited the most pronounced destabilization. Molecular dynamics simulations confirmed stability variations across mutants, with G129E exhibiting greater instability. This comprehensive analysis enhances understanding of PTEN nsSNP impacts, offering insights for therapeutic interventions and future experimental validation.

https://mbrc.shirazu.ac.ir/article_7976_c8f29197169f6719a655edd90782cb5c.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 14 3 2025 09 01 HIV-1 reverse transcriptase subtyping revealed CRF35-AD as a current subtype in the northeast of Iran 237 241 8020 10.22099/mbrc.2025.52193.2089 EN Zahra Mazaheri Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Masoud Youssefi Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Journal Article 2025 01 16 Previously, the sequence of the HIV-1 reverse transcriptase gene was analyzed to identify mutations associated with drug resistance. We statistically analyzed the relationship between a set of additional data and increasing mutations. Existing sequences were also phylogenetically analyzed. Of all patients tested for phylogenetic tree analysis, one individual had the F subtype, two had the CRF01-AE strain, and two had the A subtype. Phylogenetic tree analysis revealed that HIV-1 CRF35-AD was the most prevalent subtype (88.6%) among the cases studied. The number of treatment discontinuations (r=0.621, df=20, p=0.002) and the duration of treatment (r=0.452, df=20, p=0.035) were significantly correlated with an increase in mutations.

https://mbrc.shirazu.ac.ir/article_8020_64643ee7c2408dac3262aeca2b5afedb.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 14 3 2025 09 01 Expression patterns of circRFX3 and miR-587 in colorectal cancer patients 243 248 8027 10.22099/mbrc.2025.52016.2080 EN Samaneh Najafi Department of Biology, University Campus 2, University of Guilan, Rasht, Iran Zivar Salehi Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran Farhad Mashayekhi Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran Hamid Saidi-Saedi Department of Internal Medicine, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Journal Article 2024 12 25 Circular RNAs (circRNAs) are non-coding, single-stranded RNAs considered by their closed-loop structures. Research has established a connection between circRNAs and cancer progression. The objective of this project was to evaluate the expression levels of a newly discovered circRNA, circRFX3 (hsa_circRFX3_003), along with its target gene, miR-587. The study involved 60 patients diagnosed with Colorectal cancer (CRC) and 60 healthy individuals as controls. Total RNA was extracted from blood samples, converted into cDNA, and analyzed using qRT-PCR. The findings revealed an up-regulation of miR-587 and a down-regulation of circRFX3 in the blood samples of CRC patients. An inverse relationship was observed between the levels of miR-587 and circRFX3; however, there was no significant difference in circRFX3 expression levels between stages I+II and stages III+IV. The levels of miR-587 expression were linked to tumor size and location. Both circRFX3 and miR-587 play significant roles in the pathophysiology of CRC; however, additional research is necessary to elucidate their specific contributions to CRC development.

https://mbrc.shirazu.ac.ir/article_8027_fc74b765e3ce0720227387e57a62acc4.pdf

Shiraz University Press Molecular Biology Research Communications 2322-181X 14 3 2025 09 01 Abstracts of 7th International and 9th National IASBS Symposium on Biological Sciences; May 6 & 7, 2025; Institute for Advanced Studies in Basic Sciences, Zanjan, Iran 8172 10.22099/mbrc.2025.53750.2186 EN Mohammad Masoudi Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731, Iran Journal Article 2025 07 21 https://mbrc.shirazu.ac.ir/article_8172_1c8f9e586fa47d5f20a9fa76111a1048.pdf