Over-expression of mir-181a-3p in serum of breast cancer patients as diagnostic biomarker.

BACKGROUND: Recently, the significance of epigenetics, particularly in breast cancer (BC), has become increasingly recognized. MicroRNAs (miRNAs), as an epigenetic factor, are offering valuable insights into various aspects of BC, such as its origins and clinical features. Therefore, studying the disruption of specific miRNAs through microarray and RNA-seq techniques is considered useful. METHODS AND MATERIALS: We analyzed two microarray datasets (GSE106817 and GSE113486) in order to discover dysregulated miRNAs in the serum of BC patients. Subsequently, RNA-seq analysis was employed on the TCGA data. Two miRNAs, mir-450a-5p and mir-181a-3p, as novel miRNAs in BC studies, were selected for assessment in the serum of 100 BC patients versus 100 healthy female participants. The quantities of the miRNAs described above were determined through the utilization of RT-qPCR. Furthermore, ROC curve assessments were conducted for each individual miRNA. Next, an assessment was conducted to determine the prognostic significance of these miRNAs. CONCLUSIONS: In summary, the utilization of microarray and RNA-seq analysis techniques has demonstrated that mir-450a-5p and mir-181a-3p exhibit elevated expression levels in the serum of BC patients. However, it is noteworthy that only mir-181a-3p displayed clinical dysregulation, as confirmed by RT-PCR findings. These miRNAs have been found to play a crucial role in modulating essential cellular processes and biological functions that contribute to cancer development. Furthermore, noteworthy outcomes have been observed for mir-181a-3p in relation to diagnostic and prognostic clinical characteristics.

The hopeful anticancer role of oleuropein in breast cancer through histone deacetylase modulation.

Breast cancer (BC) is one of the most common cancers among women worldwide. Genetic, epigenetic, and environmental factors play a crucial role in BC development. Because epigenetic imbalance occurs earlier than expression in carcinogenesis and is reversible, epigenetic reprogramming strategies could be more useful for cancer prevention and therapy. There is evidence indicating that the use of herbal compounds with low toxicity can offer a real benefit in the prevention or treatment of cancer. Oleuropein (OLE), as a natural polyphenol, has shown the anticancer property in cancers. In this study, we investigated for the first time the link between histone deacetylase (HDAC) and OLE to have an anticancer effect in BC. The potential apoptotic and anti-invasive effects of OLE were tested using MCF-7 cells. Transcript expression of HDAC1 and HDAC4 genes after treatment was determined using quantitative reverse transcription polymerase chain reaction. OLE obviously reduced invasiveness and cell viability and simultaneously induced cell apoptosis in MCF-7 cancer cells. Dose-dependent reduction of HDAC4 was observed, whereas apparent changes could not be observed in HDAC1 expression. The current research indicated that OLE can inhibit proliferation and invasion of cells by inducing apoptosis likely through modulation of an important epigenetic factor, HDAC4, in MCF-7 cells. OLE has the potential to be a therapeutic drug for BC prevention and treatment.

Targeted Mutation Analysis of the SLC26A4, MYO6, PJVK and CDH23 Genes in Iranian Patients with AR Nonsyndromic Hearing Loss.

BACKGROUND: Hearing loss (HL) is the most prevalent sensory disorder. The over 100 genes implicated in autosomal recessive nonsyndromic hearing loss (ARNSHL) makes it difficult to analyze and determine the accurate genetic causes of hearing loss. We sought to de?ne the frequency of seven hearing loss-Causing causing genetic Variants in four genes in an Iranian population with hearing loss. MATERIALS AND METHODS: One hundred ARNSHL patients with normal GJB2/GJB6 genes were included, and targeted mutations in SLC26A4, MYO6, PJVK and CDH23 genes were analyzed by ARMS-PCR. The negative and positive results were confirmed by the Sanger sequencing. RESULTS: We found only two mutations, one in MYO6 (c.554-1 G > A) gene and another in PJVK (c.547C > T). CONCLUSION: c.554-1G > A and c.547C > T mutations are responsible for 1% each of the Iranian ARNSHL patients. These genes are not a frequent cause of ARNSHL in an Iranian population.

Screening for intermediate CGG alleles of FMR1 gene in male Iranian patients with Parkinsonism.

Male carriers of an expansion of CGG alleles (with 55-200 CGG repeats) in the FMR1 gene are affected with Fragile X-associated tremor/ataxia syndrome (FXTAS). On the other hand, individuals with Parkinson's disease (PD) or Parkinsonism spectrum disorders may have some clinical features that overlap with FXTAS. To investigate the possible association between PD and FMR1 expanded alleles, we screened a total of 154 male PD patients and 190 gender- and age-matched healthy control subjects from Iran. Eleven intermediate allele carriers (7.14 %) were detected among PD patients, compared with three carriers (1.57 %) among the controls (P = 0.01). No pre-mutation carriers were identified. Our results indicate that there is a potential association between FMR1 intermediate expanded alleles and PD.

The role of mir-151a-5p in tumorigenesis; A systematic review.

BACKGROUND: Highly supported microRNAs (miRNAs) are key players in cancer development. Each of these miRNAs may act as an oncomir, a tumor-suppressor, or both in various cancers. Mir-151a-5p is believed to be one of these miRNAs with diverse roles. We have conducted this systematic review to clarify the role of mir-151a-5p in formation of various cancers. METHODS AND MATERIALS: We searched for existing articles in PubMed, Web of Science, Cochrane, Scopus, and RNAcentral databases up to November 2022. A total of 23 articles were qualified and included in the present systematic review. This review is registered on JBI at https://jbi.global/systematic-review-register. Expression levels, diagnostic and prognostic values, biological processes, and targeted downstream genes are included. RESULTS: Assembled data indicate the expression levels of mir-151a-5p vary from down- to up-regulated based on the type of the cancer. Its functional role depends on the genetic profile of cancerous tissue. Results mostly point to the oncogenic role of this miRNA in Pituitary adenomas, Acute Myeloid Leukemia (AML), Endometrial, Lung, Barrett's carcinogenesis, Colorectal, Myelodysplastic syndromes, Hepatocellular carcinoma and Breast cancers, as its inhibited targets seem to be controlling several signaling pathways, cell adhesion, and cell cycle. At the same time, tumor-suppressing role has also been observed only in Malignant Pleural Mesothelioma, Central Nerve System (CNS) lymphoma, Chronic Myeloid and Acute Lymphocytic Leukemia. Two types of cancers, prostate and colon, show contradictory results as there are studies supporting both up- and down-regulation in these cancers. Pituitary adenomas, Barrett's carcinogenesis and CNS lymphomas are top cancers diagnosed with mir-151-5p. However, prognostic feature is only applicable to Lung adenocarcinoma. DISCUSSION: Based on the present findings and further studies in the future, mir-151a-5p may be used as diagnostic and prognostic biomarkers or even a therapeutic target in cancer studies. DATA AVAILABILITY STATEMENT: The articles used in this study can be found with the defined search phrase in mentioned databases. A list of selected articles will be available on reasonable requests.

WITHDRAWN: In silico and Experimental Analysis of miR-125b-5 and miR-485-5p Expression in Serum of Patients with Breast Cancer

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policiesmain. php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Restoration of correct splicing in IVSI-110 mutation of ß-globin gene with antisense oligonucleotides: implications and applications in functional assay development.

OBJECTIVES: The use of antisense oligonucleotides (AOs) to restore normal splicing by blocking the recognition of aberrant splice sites by the spliceosome represents an innovative means of potentially controlling certain inherited disorders affected by aberrant splicing. Selection of the appropriate target site is essential in the success of an AO therapy. In this study, in search for a splice model system to facilitate the evaluation of AOs to redirect defective splicing of IVSI-110 ß-globin intron, an EGFP-based IVSI-110 specific cellular reporter assay system has been developed and a number of AOs were tested in this cellular splicing assay. MATERIALS AND METHODS: A recombinant plasmid (pEGFP/I-110) carrying the EGFP gene interrupted by a mutated human ß-globin intron 1 (IVSI-110) was developed and transfected into K562 cells. A number of AOs with a 2'-O-methyl oligoribonucleotide (2'-O-Me) backbone system were systematically tested in this cellular splicing assay. RESULTS: The mutation in the intron causes aberrant splicing of EGFP pre-mRNA, preventing translation of EGFP; however, treatment of the cells with specific concentration of a sequence specific 2'-O-Me AO targeted to the aberrant splice site induced correct splicing and resulted in restoring of EGFP activity. CONCLUSION: This cellular splicing assay provides a novel functional assay system in assessing the cellular delivery efficiency of AOs and therapeutic effect of AOs in restoration of aberrant splicing.

Genotyping of Intron Inversions and Point Mutations in Exon 14 of the FVIII Gene in Iranian Azeri Turkish Families with Hemophilia A.

Hemophilia A (HA) is an inherited X-linked bleeding disorder caused by a variety of mutations that are distributed throughout the large FVIII gene (F8). The most common mutations in studied populations with severe HA are introns 22 and 1 inversions, gross exon deletions and point mutations in exon 14. The aim of this study was to define the frequency of these common mutations in Iranian population of Azeri Turkish in North West of Iran. Fifty patients with severe HA and forty-three female potential carriers were genotyped by inverse shifting polymerase chain reaction (IS-PCR), long-range PCR, multiplex PCR, and sequencing methods for the detection of Intron 22 and 1 inversions, gross exon deletions, and exon 14 point mutations, respectively. F8 intron 22 inversion was detected in 22 (44 %) out of 50 patients. Moreover, we detected one intron 1 inversion (2 %), and one point mutation in exon 14 (2 %). In this population, 52 % of the patients with hemophilia A did not show to carry a mutation in the analyzed regions by three mentioned methods. F8 intron 22 inversion was the major causative mutation in nearly 50 % of severe HA cases in an Azerbaijani Turkish population, which is similar to the incidence of other populations. IS-PCR is a robust, rapid, efficient, and cost-effective method for the genetic analysis of patients with severe HA and for HA carrier detection, especially in developing countries.

One Novel Frameshift Mutation on Exon 64 of COL7A1 Gene in an Iranian Individual Suffering Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is an extremely rare subtype of bullous dermatosis caused by the COL7A1 gene mutation. After genomic DNA extraction from the peripheral blood sample of all subjects (3 pedigree members and 3 unrelated control individuals), COL7A1 gene screening was performed by PCR amplification and direct DNA sequencing of all of the coding exons and flanking intronic regions. Genetic analysis of the COL7A1 gene in an affected individual revealed a novel mutation: c.5493delG (p.K1831Nfs*10) in exon 64 of the COL7A1 gene in homozygous state. This mutation was not discovered in 3 unrelated Iranian control individuals. These data suggest that c.5493delG may influence the phenotype of RDEB. The result of this case report contributes to the expanding database on COL7A1 mutations.

Molecular mechanisms of apoptosis and roles in cancer development and treatment.

Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis.

Detection of hemophilia a carriers in Azeri Turkish population of Iran: usefulness of HindIII and BclI markers.

Hemophilia A (HA) is an inherited X-linked coagulation disorder caused by the deficiency of factor VIII (FVIII). Linkage analysis is a common indirect method for the detection of female carriers in families with HA. In the current study, 173 patients from 30 unrelated families with HA were recruited from the Azeri Turkish population of northwest Iran and analyzed for BclI and HindIII markers by polymerase chain reaction-restriction fragment length polymorphism. We investigated the potential of using these markers for the detection of mutation in carriers through linkage analysis, which would be of tremendous use in prenatal diagnosis. Among the tested women, 47% and 35% were found to be heterozygous for BclI and HindIII polymorphic markers, respectively. The BclI and HindIII markers were informative for the detection of 63% and 17% potential carriers, respectively, demonstrating the effectiveness of the BclI marker for the detection of HA carriers among the Azeri Turkish population.

Prenatal diagnosis of spinal muscular atrophy: clinical experience and molecular genetics of SMN gene analysis in 36 cases.

INTRODUCTION: prenatal diagnosis in families at risk for spinal muscular atrophy (SMA) mainly of type 1 is often applied due to the high incidence, most severe and newborn outcome of the disease. CASE: we present our clinical experience for 36 families with history of having at least one child with homozygous deletions of the SMN1 gene between. Seventeen families requested for prenatal prediction and of these cases, 8 fetuses were diagnosed to be at risk of developing the disease and the parents decided to terminate the pregnancy. Nine fetuses were detected with no homozygous deletion of the SMN1 and reached to full term delivery. Follow-up of live born children and abortion products never led to false or negative result. CONCLUSION: therefore, application of SMN1 deletion detection by simple PCR assay in families with homozygous deletion of the SMN1 gene could be suggested for prenatal prediction in such families.