The role of miRNAs and lncRNAs in neurofibromatosis type 1

Khosravi, Teymoor; Oladnabi, Morteza

doi:10.1002/jcb.30349

Cited by 5 publications

(2 citation statements)

References 103 publications

(181 reference statements)

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“…Finally, some tumors with wild-type NF1 may also display NF1 protein reduction by posttranscriptional inhibition, such as microRNA silencing and proteasome-mediated NF1 protein degradation, but it is unlikely by epigenetic silencing through promoter methylation [ 55 , 56 , 57 ].…”

Section: Molecular Genetics Of Nf1 Inactivationmentioning

confidence: 99%

The Contribution of Oxidative Stress to NF1-Altered Tumors

et al. 2023

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The neurofibromatosis-1 gene (NF1) was initially characterized because its germline mutation is responsible for an inherited syndromic disease predisposing tumor development, in particular neurofibromas but also various malignancies. Recently, large-scale tumor sequencing efforts have demonstrated NF1 as one of the most frequently mutated genes in human cancer, being mutated in approximately 5–10% of all tumors, especially in malignant peripheral nerve sheath tumors and different skin tumors. NF1 acts as a tumor suppressor gene that encodes neurofibromin, a large protein that controls neoplastic transformation through several molecular mechanisms. On the other hand, neurofibromin loss due to NF1 biallelic inactivation induces tumorigenic hyperactivation of Ras and mTOR signaling pathways. Moreover, neurofibromin controls actin cytoskeleton structure and the metaphase–anaphase transition. Consequently, neurofibromin deficiency favors cell mobility and proliferation as well as chromosomal instability and aneuploidy, respectively. Growing evidence supports the role of oxidative stress in NF1-related tumorigenesis. Neurofibromin loss induces oxidative stress both directly and through Ras and mTOR signaling activation. Notably, innovative therapeutic approaches explore drug combinations that further increase reactive oxygen species to boost the oxidative unbalance of NF1-altered cancer cells. In our paper, we review NF1-related tumors and their pathogenesis, highlighting the twofold contribution of oxidative stress, both tumorigenic and therapeutic.

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Section: Molecular Genetics Of Nf1 Inactivationmentioning

confidence: 99%

The Contribution of Oxidative Stress to NF1-Altered Tumors

et al. 2023

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“…The research question seeks to determine the extent to which specific genetic variants contribute to the clinical features of these disorders within the Iranian population, which is characterized by a high consanguineous marriage rate [16,49]. It is hypothesized that a clear genetic basis of these diseases can aid in the development of more precise diagnostic and therapeutic strategies like whole-exome sequencing or RNA therapeutics [5,22]. The genetic diversity of the Iranian population is leveraged in this study to fill a critical knowledge gap in understanding the pathogenesis of these syndromes and to propose potential targets for intervention in populations with similar genetic backgrounds.…”

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confidence: 99%

In silico analysis of mutation spectrum of Ehlers–Danlos, osteogenesis imperfecta, and cutis laxa overlapping phenotypes in Iranian population

Khosravi,

Naghipoor,

Vaghefi

et al. 2024

Egypt J Med Hum Genet

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Background Ehlers–Danlos syndrome (EDS), osteogenesis imperfecta (OI), and cutis laxa (CL) are three rare and heterogeneous connective tissue disorders. Patients with these syndromes have similar manifestations and unpredictable prognosis, making a misdiagnosis highly probable. Some of their subtypes are inherited in autosomal recessive patterns, so they are expected to be prevalent in populations like Iran, where consanguineous marriages are common. In the current work, a cohort of Iranian patients with overlapping phenotypes of the EDS/OI/CL and their mutation spectrum was defined. Based on this, in silico analysis was conducted to anticipate further probable genetic variations. Pathogenicity of EDS, OI, and CL variants in Iranian patients was evaluated using Web servers. A protein interaction network was created by String database and visualized using a Python-based library. The Iranome database was used to predict other genetic mutations in all reported genes of EDS, OI, and CL syndromes. Results In the EDS/OI/CL overlap phenotype, 32 variants in 18 genes have been involved. At least 59% of patients were from families with consanguineous marriages. Interaction analysis showed that COL1A1, COL1A2, CRTAP, LEPRE1, PLOD1, and ADAMTS2 have the most significant impact within the protein network of EDS/OI/CL overlap phenotype. Analyzing the Iranome database revealed 46 variants of EDS, OI, and CL genes potentially disease causing. Conclusion The overlapping phenotype of EDS, OI, and CL syndromes requires genetic testing (e.g., whole-exome sequencing) to reveal respective variants, which helps to diagnose more accurately and manage the disease more effectively. Particularly in populations with high rates of consanguineous marriages, such as Iran, genetic screening plays a crucial role in premarital and prenatal counseling to prevent the transmission of these rare connective tissue disorders.

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