Inhibitor of Growth Factors Regulate Cellular Senescence

Simple Summary Five members of the Inhibitor of Growth (ING) family share a highly conserved plant homeodomian with affinity to the specific histone modification H3K4me3. Since some ING family members are preferentially associated with histone acetyltransferaseactivity while other members with histone deacetlyse activity, the ING family membres are epigenetic regulators. Interestingly, ING members can regulate the induction cellular senescence in both primray untransformed human cells as well as human cancer cells. We discuss here the up-to-date knowledge about their regulatory activity within the cellular senescent program. Abstract The Inhibitor of Growth (ING) proteins are a group of tumor suppressors with five conserved genes. A common motif of ING factors is the conserved plant homeodomain (PHD), with which they bind to chromatin as readers of the histone mark trimethylated histone H3 (H3K4me3). These genes often produce several protein products through alternative splicing events. Interestingly, ING1 and ING2 participate in the establishment of the repressive mSIN3a-HDAC complexes, whereas ING3, ING4, and ING5 are associated with the activating HAT protein complexes. In addition to the modulation of chromatin’s structure, they regulate cell cycle transition, cellular senescence, repair of DNA damage, apoptosis, and angiogenic pathways. They also have fundamental effects on regulating cellular senescence in cancer cells. In the current review, we explain their role in cellular senescence based on the evidence obtained from cell line and animal studies, particularly in the context of cancer

Limb Girdle Muscular Dystrophy Type 2E Due to a Novel Large Deletion in SGCB Gene

How to Cite This Article: Ghafouri-Fard S, Hashemi-Gorji F, Fardaei M, Miryounesi M. Limb Girdle Muscular Dystrophy Type 2E Due to a Novel Large Deletion in SGCB Gene. Iran J Child Neurol. Summer 2017; 11(3):57-60.  AbstractAutosomal recessive limb-girdle muscular dystrophies (LGMD type 2) are a group of clinically and genetically heterogeneous diseases with the main characteristics of weakness and wasting of the pelvic and shoulder girdle muscles. Among them are sarcoglycanopathies caused by mutations in at least four genes named SGCA, SGCB, SGCG and SGCD. Here we report a consanguineous Iranian family with two children affected with LGMD type 2E.Mutation analysis revealed a novel homozygous exon 2 deletion of SGCB gene in the patients with the parents being heterozygous for this deletion. This result presents a novel underlying genetic mechanism for LGMD type 2E.References1. Lo HP, Cooper ST, Evesson FJ, Seto JT, Chiotis M, Tay V et al. Limb-girdle muscular dystrophy: diagnostic evaluation, frequency and clues to pathogenesis. Neuromuscul Disord 2008;18(1):34-44.2. Bushby KM, Beckmann JS. The 105th ENMC sponsored workshop: pathogenesis in the non-sarcoglycan limbgirdle muscular dystrophies, Naarden, April 12-14, 2002. Neuromuscul Disord 2003;13(1):80-90.3. Zatz M, de Paula F, Starling A, Vainzof M. The 10 autosomal recessive limb-girdle muscular dystrophies. Neuromuscul Disord 2003;13(7-8):532-44.4. Araishi K, Sasaoka T, Imamura M, Noguchi S, Hama H, Wakabayashi E et al. Loss of the sarcoglycan complex and sarcospan leads to muscular dystrophy in beta-sarcoglycan-deficient mice. Hum Mol Genet 1999;8(9):1589-98.5. Pegoraro E, Hoffman EP. Limb-girdle muscular dystrophy overview. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. 2012.6. Straub V, Bushby K. The childhood limb-girdle muscular dystrophies. Semin Pediatr Neurol 2006;13(2):104-14.7. Kaindl AM, Jakubiczka S, Lucke T, Bartsch O, Weis J, Stoltenburg-Didinger G, et al. Homozygous microdeletion of chromosome 4q11-q12 causes severe limb-girdle muscular dystrophy type 2E with joint hyperlaxity and contractures. Hum Mut 2005;26(3):279- 80.8. Trabelsi M, Kavian N, Daoud F, Commere V, Deburgrave N, Beugnet C et al. Revised spectrum of mutations in sarcoglycanopathies. European journal of human genetics. Europ J Hum Gene 2008;16(7):793- 803.9. Rivas E, Teijeira S, dos Santos MR, Porrit I, Leturcq F, Fernandez JM et al. Beta-sarcoglycanopathy (LGMD 2E) in a Spanish family. Acta Myol 2004;23(3):159-62.10. Barresi R, Di Blasi C, Negri T, Brugnoni R, Vitali A, Felisari G et al. Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by beta sarcoglycan mutations. J Med Gene 2000;37(2):102-7

Regulatory Role of Non-Coding RNAs on Immune Responses During Sepsis

Sepsis is resulted from a systemic inflammatory response to bacterial, viral, or fungal agents. The induced inflammatory response by these microorganisms can lead to multiple organ system failure with devastating consequences. Recent studies have shown altered expressions of several non-coding RNAs such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) during sepsis. These transcripts have also been found to participate in the pathogenesis of multiple organ system failure through different mechanisms. NEAT1, MALAT1, THRIL, XIST, MIAT and TUG1 are among lncRNAs that participate in the pathoetiology of sepsis-related complications. miR-21, miR-155, miR-15a-5p, miR-494-3p, miR-218, miR-122, miR-208a-5p, miR-328 and miR-218 are examples of miRNAs participating in these complications. Finally, tens of circRNAs such as circC3P1, hsa_circRNA_104484, hsa_circRNA_104670 and circVMA21 and circ-PRKCI have been found to affect pathogenesis of sepsis. In the current review, we describe the role of these three classes of noncoding RNAs in the pathoetiology of sepsis-related complications

The emerging role of non-coding RNAs in pituitary gland tumors and meningioma

Simple Summary Non-coding RNAs have been recently attained attention because of their contribution in the pathogenesis of brain tumors. These transcripts have been shown to be dysregulated in pituitary gland tumors as well as meningiomas. In these two types of brain tumors, dysregulation of non-coding RNAs has been associated with some clinical features and response to therapeutic options. Different types of non-coding RNAs have been shown to interact with each other to promote progression of brain tumors. Further research is needed to find the possible application of non-coding RNAs as biomarkers for pituitary gland tumors as well as meningiomas, particularly in patients’ follow-up. Abstract Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are non-coding transcripts which are involved in the pathogenesis of pituitary gland tumors. LncRNAs that participate in the pathogenesis of pituitary gland tumors mainly serve as sponges for miRNAs. CLRN1-AS1/miR-217, XIST/miR-424-5p, H19/miR-93a, LINC00473/miR-502-3p, SNHG7/miR-449a, MEG8/miR-454-3p, MEG3/miR-23b-3p, MEG3/miR-376B-3P, SNHG6/miR-944, PCAT6/miR-139-3p, lncRNA-m433s1/miR-433, TUG1/miR-187-3p, SNHG1/miR-187-3p, SNHG1/miR-302, SNHG1/miR-372, SNHG1/miR-373, and SNHG1/miR-520 are identified lncRNA/miRNA pairs that are involved in this process. Hsa_circ_0001368 and circOMA1 are two examples of circRNAs that contribute to the pathogenesis of pituitary gland tumors. Meanwhile, SNHG1, LINC00702, LINC00460, and MEG3 have been found to partake in the pathogenesis of meningioma. In the current review, we describe the role of non-coding RNAs in two types of brain tumors, i.e., pituitary tumors and meningioma

Association of a Novel Nonsense Mutation in KIAA1279 with Goldberg-Shprintzen Syndrome

How to Cite This Article: Salehpour Sh, Hashemi-Gorji F, Soltani Z, Ghafouri-Fard S, Miryounesi M. Association of a Novel Nonsense Mutation in KIAA1279 with Goldberg-Shprintzen Syndrome. Iran J Child Neurol. Winter 2017; 11(1):70-74.AbstractGoldberg-Shprintzen syndrome (OMIM 609460) (GOSHS) is an autosomal recessive multiple congenital anomaly syndrome distinguished by intellectual disability, microcephaly, and dysmorphic facial characteristics. Most affected individuals also have Hirschsprung disease and/or gyral abnormalities of the brain. This syndrome has been associated with KIAA1279 gene mutations at 10q22.1. Here we report a 16 yr old male patient referred to Center for Comprehensive Genetic Services, Tehran, Iran in 2015 with cardinal features of GOSHS in addition to refractory seizures. Whole exome sequencing in the patient revealed a novel nonsense (stop gain) homozygous mutation in KIAA1279 gene (KIAA1279: NM_015634:exon6:c.C976T:p.Q326X).Considering the wide range of phenotypic variations in GOSHS, relying on phenotypic characteristics for discrimination of GOSH from similar syndromes may lead to misdiagnosis. Consequently, molecular diagnostic tools would help in accurate diagnosis of such overlapping phenotypes.References1. Goldberg R, Shprintzen R. Hirschsprung megacolon and cleft palate in two sibs. J Craniofac Genet Dev Biol 1980;1(2):185-9. 2. Yomo A, Taira T, Kondo I. Goldberg-Shprintzen syndrome: Hirschsprung disease, hypotonia, and ptosis in sibs. Am J Med Genet 1991;41(2):188-91.3. Drevillon L, Megarbane A, Demeer B, Matar C, Benit P, Briand-Suleau A, et al. KBP-cytoskeleton interactions underlie developmental anomalies in Goldberg-Shprintzen syndrome. Hum Mol Genet 2013;22(12):2387-99.4. Brooks AS, Bertoli-Avella AM, Burzynski GM, Breedveld GJ, Osinga J, Boven LG, et al. Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems. Am J Med Genet 2005;77(1):120-6.5. Blatch GL, Lassle M. The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. BioEssays 1999;21(11):932-9.6. Alves MM, Burzynski G, Delalande J-M, Osinga J, van der Goot A, Dolga AM, et al. KBP interacts with SCG10, linking Goldberg–Shprintzen syndrome to microtubule dynamics and neuronal differentiation. Hum Mol Genet 2010:ddq280.7. Valence S, Poirier K, Lebrun N, Saillour Y, Sonigo P, Bessières B, et al. Homozygous truncating mutation of the KBP gene, encoding a KIF1B-binding protein, in a familial case of fetal polymicrogyria. Neurogenetics2013;14(3-4):215-24.8. Murphy HR, Carver MJ, Brooks AS, Kenny SE, Ellis IH. Two brothers with Goldberg-Shprintzen syndrome. Clinl Dysmorphol 2006;15(3):165-9

Interaction Between Non-Coding RNAs and Interferons: With an Especial Focus on Type I Interferons

Interferons (IFNs) are a group of cellular proteins with critical roles in the regulation of immune responses in the course of microbial infections. Moreover, expressions of IFNs are dysregulated in autoimmune disorders. IFNs are also a part of immune responses in malignant conditions. The expression of these proteins and activities of related signaling can be influenced by a number of non-coding RNAs. IFN regulatory factors (IRFs) are the most investigated molecules in the field of effects of non-coding RNAs on IFN signaling. These interactions have been best assessed in the context of cancer, revealing the importance of immune function in the pathoetiology of cancer. In addition, IFN-related non-coding RNAs may contribute to the pathogenesis of neuropsychiatric conditions, systemic sclerosis, Newcastle disease, Sjögren’s syndrome, traumatic brain injury, lupus nephritis, systemic lupus erythematosus, diabetes mellitus, and myocardial ischemia/reperfusion injury. In the current review, we describe the role of microRNAs and long non-coding RNAs in the regulation of IFN signaling

A Review on the Role of Non-Coding RNAs in the Pathogenesis of Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune condition related to autoantibodies against certain proteins in the postsynaptic membranes in the neuromuscular junction. This disorder has a multifactorial inheritance. The connection between environmental and genetic factors can be established by epigenetic factors, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). XLOC_003810, SNHG16, IFNG-AS1, and MALAT-1 are among the lncRNAs with a possible role in the pathoetiology of MG. Moreover, miR-150-5p, miR-155, miR-146a-5p, miR-20b, miR-21-5p, miR-126, let-7a-5p, and let-7f-5p are among miRNAs whose roles in the pathogenesis of MG has been assessed. In the current review, we summarize the impact of miRNAs and lncRNAs in the development or progression of MG

Emerging role of non-coding RNAs in regulation of t-lymphocyte function

T-lymphocytes (T cells) play a major role in adaptive immunity and current immune checkpoint inhibitor-based cancer treatments. The regulation of their function is complex, and in addition to cytokines, receptors and transcription factors, several non-coding RNAs (ncRNAs) have been shown to affect differentiation and function of T cells. Among these non-coding RNAs, certain small microRNAs (miRNAs) including miR-15a/16-1, miR-125b-5p, miR-99a-5p, miR-128-3p, let-7 family, miR-210, miR-182-5p, miR-181, miR-155 and miR-10a have been well recognized. Meanwhile, IFNG-AS1, lnc-ITSN1-2, lncRNA-CD160, NEAT1, MEG3, GAS5, NKILA, lnc-EGFR and PVT1 are among long non-coding RNAs (lncRNAs) that efficiently influence the function of T cells. Recent studies have underscored the effects of a number of circular RNAs, namely circ_0001806, hsa_circ_0045272, hsa_circ_0012919, hsa_circ_0005519 and circHIPK3 in the modulation of T-cell apoptosis, differentiation and secretion of cytokines. This review summarizes the latest news and regulatory roles of these ncRNAs on the function of T cells, with widespread implications on the pathophysiology of autoimmune disorders and cancer

Interaction between Non-Coding RNAs and Androgen Receptor with an Especial Focus on Prostate Cancer

The androgen receptor (AR) is a member of the nuclear receptor superfamily and has three functional domains, namely the N-terminal, DNA binding, and C-terminal domain. The N-terminal domain harbors potent transactivation functions, whereas the C-terminal domain binds to androgens and antiandrogens used to treat prostate cancer. AR has genomic activity being DNA binding-dependent or through interaction with other DNA-bound transcription factors, as well as a number of non-genomic, non-canonical functions, such as the activation of the ERK, AKT, and MAPK pathways. A bulk of evidence indicates that non-coding RNAs have functional interactions with AR. This type of interaction is implicated in the pathogenesis of human malignancies, particularly prostate cancer. In the current review, we summarize the available data on the role of microRNAs, long non-coding RNAs, and circular RNAs on the expression of AR and modulation of AR signaling, as well as the effects of AR on their expression. Recognition of the complicated interaction between non-coding RNAs and AR has practical importance in the design of novel treatment options, as well as modulation of response to conventional therapeutics