Crosstalk between long non-coding RNAs and p53 signaling pathway in colorectal cancer: A review study.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and the third leading cause of cancer-related fatalities. Long non-coding RNAs (lncRNAs) are key regulators of diverse physiological processes and are dysregulated in a wide range of pathophysiological circumstances such as CRC. Studies revealed that aberrant expressions of lncRNAs clearly modulate the expression level of p53 gene in CRC, thereby transactivating multiple downstream pathways. P53 is regarded as a crucial tumor suppressor gene which promotes cell-cycle arrest, DNA repair, senescence or apoptosis in response to cellular stresses. P53 is also mutated in CRC as well as various types of human malignancies. Therefore, lncRNAs interact with the p53 signaling pathway in numerus ways and significantly influence CRC-related processes. The current findings in the investigation of the crosstalk between lncRNAs and the P53 pathway in controlling CRC carcinogenesis, tumor progression, and therapeutic resistance are summarized in the this review. A deeper knowledge of CRC carcinogenesis may also have implications in CRC prevention and treatment through more research.

Prediction of Potential Drug Targets and Vaccine Candidates Against Antibiotic-Resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the leading causes of nosocomial infections, characterized by increasing antibiotic resistance, severity and mortality. Therefore, numerous efforts have been made nowadays to identify new therapeutic targets. This study aimed to find potential drug targets and vaccine candidates in drug-resistant strains of P. aeruginosa. Extensive antibiotic-resistant and carbapenem-resistant strains of P. aeruginosa with complete genome were selected and ten common hypothetical proteins (HPs) containing more than 200 amino acids were obtained. The structural, functional and immunological predictions of these HPs were performed with the utility of bioinformatics approaches. Two common HPs (Gene ID: 2877781645 and 2877781936) among other investigated proteins were revealed as potential candidates for pharmaceutical and vaccine purposes based on structural and physicochemical properties, functional domains, subcellular localizations, signal peptides, toxicity, virulence factor, antigenicity, allergenicity and immunoinformatic predictions. The consequence of this predictive study will assist in novel drug and vaccine design through experimental investigations.

Competing Endogenous RNAs (ceRNAs) in Colorectal Cancer: A Review.

Colorectal cancer (CRC) is a common type of cancer and the second leading cause of cancer-related deaths worldwide. Competing endogenous RNAs (ceRNAs) that contain microRNA response elements (MREs) are involved in CRC progression. They can compete with microRNAs (miRNAs) via their MREs, which can combine non-coding and coding RNAs via complex ceRNA networks. This molecular interaction has the potential to affect a wide variety of biological processes, and many cancers can occur as a result of an imbalanced ceRNA network. Recent research indicates that numerous dysregulated RNAs in CRC may function as ceRNAs, regulating multiple biological functions of the tumour, including proliferation, apoptosis, metastasis, invasion and migration. In this review, we discuss the role of protein-coding and non-coding RNAs, such as long non-coding RNAs, circular RNAs and pseudogenes, in the occurrence of ceRNA networks in CRC, and their function in cancer-related pathways, such as Wnt/ß-catenin, mitogen-activated protein kinase and transforming growth factor-ß signalling pathways. Additionally, we discuss validated ceRNAs associated with CRC biological functions and their potential role as novel prognostic and diagnostic biomarkers. Examining the role of ceRNAs in CRC sheds new light on cancer treatment and pathogenesis.

Detection of TET2 Mutation in Patients with De Novo Acute Myeloid Leukemia: A Mutation Analysis of 51 Iranian Patients.

Acute myeloid leukemia (AML) is a heterogeneous clonal disease that is considered to originate from hematopoietic stem cells, which are characterized by impaired myelopoiesis and blast proliferation. TET oncogene family member 2 (TET2) mutations are frequent in myeloid malignancies and several studies have assessed the clinical importance of TET2 mutations. However, its frequency ratio has not yet been fully clarified. METHOD: Hence, our study was aimed to analyze TET2mut in patients with de-novo AML and their association with clinical, molecular characteristics and Nucleophosmin 1 (NPM1), Fms-like tyrosine kinase 3 (FLT3), CCAAT Enhancer Binding Protein Alpha (CEBPA) and Wilms' tumor protein (WT1) gene expression. Fifty-one Iranian patients were screened by polymerase chain reaction (PCR) and direct sequencing to evaluate TET2 mutations frequency. RESULTS: Out of all patients, 10 mutations in 8 patients (15.6%) were detected and closely associated with higher age and higher hemoglobin levels (p-value <0.05). Although FLT3, NPM1 and CEBPA gene expression did not show any significant correlation with TET2mut, cytogenetically normal acute myeloid leukemia (CN-AML)  patients appear to bear TET2mut more frequently with lower platelet counts. Monocyte-lineages leukemia has seemed to be more linked with TET2mut in these patients. CONCLUSION: Our study suggests the frequency of TET2mut in our study (15.6%) is in line with previous studies and reveals the critical role of TET2 in myeloid transformation, especially in leukemia with monocytic subtypes. 
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Characterization and haplotype study of 6 novel STR markers related to the KCNQ1 gene in heterogeneous cardiovascular disorders in the Iranian population

Background/aim: The KCNQ1 gene has a significant role in long QT syndrome, Jervell and Lange-Nielsen syndrome, familial atrial fibrillation, and short QT syndrome. Analyzing such heterogeneous disorders, six novel short tandem repeat (STR) markers around the KCNQ1 gene were found and evaluated in a healthy population, and other statistical traits of the markers were detected. Materials and methods: Using Tandem Repeats Finder (TRF) and Sequence-Based Estimation of Repeat Variability (SERV) software, STR markers were detected with valid tetra- and pentanucleotide repeats. The markers were investigated for a total of 60 unrelated Iranian healthy individuals and analyzed using GenAlEx 6.502 and Cervus 3.0.7. Results: A total of 77 haplotypes was detected, of which 25 haplotypes were unique and the others occurred at least two times. The number of haplotypes per locus ranged from 7 to 18 with the highest frequency of 69.2%, and the observed heterozygosity was calculated as 0.589. The power of discrimination ranged from 0.70 to 0.96. Five of the markers meet Hardy­Weinberg equilibrium. Conclusion: A novel panel of STR markers was described with high allele heterozygosity and segregation in every locus, which may lead to faster and more credible recognition of the disease-inducing KCNQ1 gene and allow it to be used for human identity testing and prenatal diagnosis.

Identification of a Novel KCNQ1 Frameshift Mutation and Review of the Literature among Iranian Long QT Families

Background: Long QT syndrome (LQTS) is characterized by the prolongation of QT interval, which results in syncope and sudden cardiac death in young people. KCNQ1 is the most common gene responsible for this syndrome. Methods: Molecular investigation was performed by DNA Sanger sequencing in Iranian families with a history of syncope. In silico examinations were performed for predicting the pathogenicity of the novel variant. Results: A novel homozygous KCNQ1 frameshift mutation, c.1426_1429delATGC (M476Pfs*4), was identified, and then the current literatures of five patients were reviewed regarding the LQTS. Conclusion: The novel frameshift mutation has been reported for the first time among the Iranian population. Our finding along with the case series study of LQTS patients illustrates the importance of genetic and case series in precise detection of the frequency of LQTS carriers.

Detection of a new KCNQ1 frameshift mutation associated with Jervell and Lange-Nielsen syndrome in 2 Iranian families.

Jervell-Lange Nielsen syndrome (JLNS) with autosomal recessive inheritance is a congenital cardiovascular disorder characterized by prolongation of QT interval on the ECG and deafness. We have performed molecular investigation by haplotype analysis and DNA Sanger sequencing in 2 unrelated Iranian families with a history of syncope. Mutational screening of KCNQ1 gene revealed the novel homozygous frameshift mutation c.733-734delGG (p.G245Rfs*39) in 2 obviously unrelated cases of JLNS which is probably a founder mutation in Iran. The novel mutation detected in this study is the first time reported among Iranian population and will be beneficial in the tribe and region-specific cascade screening of LQTS in Iran.

Novel frameshift mutation in the KCNQ1 gene responsible for Jervell and Lange-Nielsen syndrome.

OBJECTIVES: Jervell and Lange-Nielsen syndrome is an autosomal recessive disorder caused by mutations in KCNQ1 or KCNE1 genes. The disease is characterized by sensorineural hearing loss and long QT syndrome. MATERIALS AND METHODS: Here we present a 3.5-year-old female patient, an offspring of consanguineous marriage, who had a history of recurrent syncope and congenital sensorineural deafness. The patient and the family members were screened for mutations in KCNQ1 gene by linkage analysis and DNA sequencing. RESULTS: DNA sequencing showed a c.1532_1534delG (p. A512Pfs*81) mutation in the KCNQ1 gene in homozygous form. The results of short tandem repeat (STR) markers showed that the disease in the family is linked to the KCNQ1 gene. The mutation was confirmed in the parents in heterozygous form. CONCLUSION: This is the first report of this variant in KCNQ1 gene in an Iranian family. The data of this study could be used for early diagnosis of the condition in the family and genetic counseling.

Identification and characterization of a novel recessive KCNQ1 mutation associated with Romano-Ward Long-QT syndrome in two Iranian families.

BACKGROUND: One of the foremost causes of sudden cardiac death in the young is an inherent cardiac arrhythmia known as Long-QT syndrome (LQTS). Whereas heterozygous mutations typically lead to the Romano-Ward type of LQTS, We have provided a further evidence for the recessive transmission of a novel KCNQ1 gene mutation in two consanguineous families for the first time in Iran. METHODS: Next generation sequencing, DNA Sanger sequencing and haplotype analysis were performed for genotype determination. Twelve different in silico tools were used for predicting the variant pathogenecity along with the family and population study. RESULTS: A novel recessive KCNQ1 variant (p.D564G) was revealed in none of the unrelated healthy individuals but four patients in two apparently unrelated families. The variant was classified as a likely pathogenic mutation by combining the resulted criteria for the changed amino acid. CONCLUSIONS: Identification of the novel mutation not only supports the genetic testing as a definitive diagnostic tool for detection of at risk family members, but also emphasizes its screening in Iranian LQTS patients as this mutation is very likely a founder mutation in Iran.

Design of a biological method for rapid detection of presence of PCR inhibitors in aged bone DNA.

BACKGROUND: Molecular human identification is one of the most important tests performed in forensic laboratories. Some of these tests are applied for identification of human remains from natural disasters, wars, etc., but problems may occur as a result of DNA degradation and external DNA contamination. We investigated effects of bacterial DNA on identifying the presence or absence of PCR inhibitors in aged bone DNA. METHODS: DNA samples were extracted from blood, bone remains and Escherichia coli. These DNA were amplified using human and bacterial specific primers. RESULTS: Using different blood, aged bone, and bacterial DNA dilutions along with PCR based methods; we checked their positive, negative effects, or detecting presence of inhibitors in aged bone DNA by PCR method. CONCLUSIONS: Our observation indicated that the addition of bacterial DNA could be a valid biological method for testing the quality of bone DNA to enable us to obtain a usable profile for the identification of human remains. This method will help to test the presence of inhibitors, quantity or even quality of DNA which are of importance in profiling archeological remains. Our method will help to determine if PCR failure is due to presence of inhibitors or lack of amplifiable DNA either because of degradation, minute amount or absence of human DNA.