ABSTRACT
Long non-coding RNAs (lncRNAs) are transcripts with a length of usually more than 200 nucleotides (nt) that have promised functions in varied biological processes. lncRNAs participate in the regulation of differentiation, development, and function of the brain. Thus, their dysregulation might play important roles in the etiology of neurological disorders such as BD. In this study, the expression level of PCAT-1, PCAT-29, and MER11C lncRNAs was evaluated in the blood of BD patients compared to the control group. Peripheral blood mononuclear cells of 50 BD type I patients and 50 healthy individuals were isolated. The RNAs were extracted and cDNA was synthesized. Then, the expression level of the desired lncRNAs was measured through Real-Time PCR. The expression levels of PCAT-29 and MER11C lncRNAs were significantly lower in BD patients compared to controls. However, the expression level of PCAT-1 was not significantly different between these two sets of samples. According to the ROC curve, PCAT-29 and MER11C had significant diagnostic power for the differentiation of BD patients from controls. Taken together, our results indicate dysregulation of two lncRNAs in patients with BD and the possible roles of these lncRNAs in the neuropathology of bipolar disorder.
Subject(s)
Bipolar Disorder , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/blood , Bipolar Disorder/genetics , Male , Female , Adult , Middle Aged , Case-Control Studies , Leukocytes, Mononuclear/metabolismABSTRACT
Background: Leishmania is a vector-borne protozoon, which causes visceral, cutaneous and mucocutaneous leishmaniosis in human and animals. Monocyte-derived exosome vaccines can be used as prophylaxis and immunotherapy strategies. The aim of this study was to design a multiple-epitope candidate vaccine using leishmaniolysin (GP63) and rK39 proteins against Leishmania major and L. infantum for monocyte-derived exosome preparation. Methods: This study was carried out in Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran, 2023-2024. Effective immunodominant epitopes were selected from two antigenic proteins of GP63 and rK39 using various immunoinformatics and bioinformatics approaches. Vibrio cholerae ß-subunit was used as an adjuvant to stimulate immune responses. Then, appropriate linkers were selected for the fusion of epitopes. The 3D model of candidate vaccine was predicted and validated. Results: This designed candidate vaccine could effectively be used as a prophylaxis strategy against leishmaniosis. Conclusion: A candidate vaccine was designed using bioinformatic and immunoinformatic studies with virtual acceptable quality; however, effectiveness of this vaccine should be verified through further in-vitro and in-vivo studies.
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The biosynthesis of novel nanoparticles with varied morphologies, which has good implications for their biological capabilities, has attracted increasing attention in the field of nanotechnology. Bioactive compounds present in the extract of fungi, bacteria, plants and algae are responsible for nanoparticle synthesis. In comparison to other biological resources, brown seaweeds can also be useful to convert metal ions to metal nanoparticles because of the presence of richer bioactive chemicals. Carbohydrates, proteins, polysaccharides, vitamins, enzymes, pigments, and secondary metabolites in brown seaweeds act as natural reducing, capping, and stabilizing agents in the nanoparticle's synthesis. There are around 2000 species of seaweed that dominate marine resources, but only a few have been reported for nanoparticle synthesis. The presence of bioactive chemicals in the biosynthesized metal nanoparticles confers biological activity. The biosynthesized metal and non-metal nanoparticles from brown seaweeds possess different biological activities because of their different physiochemical properties. Compared with terrestrial resources, marine resources are not much explored for nanoparticle synthesis. To confirm their morphology, characterization methods are used, such as absorption spectrophotometer, X-ray diffraction, Fourier transforms infrared spectroscopy, scanning electron microscope, and transmission electron microscopy. This review attempts to include the vital role of brown seaweed in the synthesis of metal and non-metal nanoparticles, as well as the method of synthesis and biological applications such as anticancer, antibacterial, antioxidant, anti-diabetic, and other functions.
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Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to prescribed medications for these illnesses. However, there is a technology called CRISPR/Cas9, which uses RNA to guide DNA targeting. This technology has revolutionized our ability to manipulate and visualize the genome, leading to advancements in research and treatment development. It can effectively reverse epigenetic alterations that contribute to drug resistance. Some studies focused on health have shown that targeting genes using CRISPR/Cas9 can be challenging when it comes to reducing drug resistance in patients with respiratory disorders. Nevertheless, it is important to acknowledge the limitations of this technology, such as off-target effects, immune system reactions to Cas9, and challenges associated with delivery methods. Despite these limitations, this review aims to provide knowledge about CRISPR/Cas9 genome editing tools and explore how they can help overcome resistance in patients with respiratory disorders. Additionally, this study discusses concerns related to applications of CRISPR and provides an overview of successful clinical trial studies.
Subject(s)
CRISPR-Cas Systems , Gene Editing , Humans , Gene Editing/methods , CRISPR-Cas Systems/genetics , Drug Resistance/genetics , Animals , Respiration Disorders/genetics , Respiration Disorders/therapy , Respiration Disorders/drug therapy , Respiratory Tract Diseases/genetics , Respiratory Tract Diseases/drug therapy , Respiratory Tract Diseases/therapyABSTRACT
Colorectal cancer (CRC) stands second in terms of mortality and third among the highest prevalent kinds of cancer globally. CRC prevalence is rising in moderately and poorly developed regions and is greater in economically advanced regions. Despite breakthroughs in targeted therapy, resistance to chemotherapeutics remains a significant challenge in the long-term management of CRC. Circular RNAs (circRNAs) have been involved in growing cancer therapy resistance, particularly in CRC, according to an increasing number of studies in recent years. CircRNAs are one of the novel subclasses of non-coding RNAs, previously thought of as viroid. According to studies, circRNAs have been recommended as biological markers for therapeutic targets and diagnostic and prognostic purposes. That is particularly notable given that the expression of circRNAs has been linked to the hallmarks of CRC since they are responsible for drug resistance in CRC patients; thereby, circRNAs are significant for chemotherapy failure. Moreover, knowledge concerning circRNAs remains relatively unclear despite using all these advanced techniques. Here, in this study, we will go over the most recent published work to highlight the critical roles of circRNAs in CRC development and drug resistance and highlight the main strategies to overcome drug resistance to improve clinical outcomes.
Subject(s)
Colorectal Neoplasms , Drug Resistance, Neoplasm , RNA, Circular , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , RNA, Circular/genetics , Drug Resistance, Neoplasm/genetics , Biomarkers, Tumor/genetics , Antineoplastic Agents/therapeutic use , Gene Expression Regulation, NeoplasticABSTRACT
Double-layer dermal substitutes (DS) generally provide more effective therapeutic outcomes than single-layer substitutes. The architectural design of DS incorporates an outer layer to protect against bacterial invasions and maintain wound hydration, thereby reducing the risk of infection and the frequency of dressing changes. Moreover, the outer layer is a mechanical support for the wound, preventing undue tension in the affected area. A 3D-printed polycaprolactone (PCL) membrane was utilized as the outer layer to fabricate DS wound dressing. Simultaneously, a polyvinyl alcohol/chitosan/sildenafil citrate (PVA/CS/SC) scaffold was electrospun onto the PCL membrane to facilitate cellular adhesion and proliferation. Scanning electron microscopy (SEM) analysis of the PCL filaments revealed a consistent cross-sectional surface and structure, with an average diameter of 562.72⯱â¯29.15⯵m. SEM results also demonstrated uniform morphology and beadless structure for the PVA/CS/SC scaffold, with an average fiber diameter of 366.77⯱â¯1.81â¯nm for PVA/CS. The addition of SC led to an increase in fiber diameter while resulting in a reduction in tensile strength. However, drug release analysis indicated that the SC release from the sample can last up to 72â¯h. Animal experimentation confirmed that DS wound dressing positively accelerated wound closure and collagen deposition in the Wistar rat skin wound model.
Subject(s)
Bandages , Chitosan , Polyesters , Polyvinyl Alcohol , Printing, Three-Dimensional , Sildenafil Citrate , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Polyvinyl Alcohol/chemistry , Animals , Polyesters/chemistry , Wound Healing/drug effects , Rats , Sildenafil Citrate/pharmacology , Sildenafil Citrate/chemistry , Membranes, Artificial , Male , Tissue Scaffolds/chemistry , Drug Liberation , Tensile StrengthABSTRACT
Brucellosis poses a significant challenge in the medical field as a systemic infection with a propensity for relapse. This study presented a novel approach to brucellosis treatment, enhancing the efficacy of doxycycline and rifampicin through the use of poly (lactic-co-glycolic) acid coupled with cadmium-telluride quantum dots (Dox-Rif-PLGA@CdTe). The double emulsion solvent evaporation method was employed to prepare Dox-Rif-PLGA@CdTe. The study scrutinized the physicochemical attributes of these nanoparticles. The impact of antibiotic-loaded nanoparticles on Brucella melitensis was evaluated through well diffusion, minimum inhibitory concentration (MIC), and cell culture. The chemical analysis results demonstrated a possibility of chemical reactions occurring among the constituents of nanoparticles. Assessments using the well diffusion and MIC methods indicated that the impact of free drugs and nanoparticles on bacteria was equivalent. However, the drug-loaded nanoparticles significantly decreased the colony-forming units (CFUs) within the cell lines compared to free drugs. In conclusion, the synthesis of nanoparticles adhered to environmentally friendly practices and demonstrated safety. The sustained drug release over 100 h facilitated drug accumulation at the bacterial site, resulting in a heightened therapeutic effect on B. melitensis and improved outcomes in brucellosis treatment. The application of these synthesized nanodrugs exhibited promising therapeutic potential.
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BACKGROUND: Current studies have shown emerging roles of lncRNAs in the pathobiology of neuropathic pain and migraine. METHODS: We have chosen five lncRNAs, namely, PVT1, DSCAM-AS, MEG3, LINC-ROR, and SPRY4-IT1 for assessment of their expression in the circulation of migraineurs. RESULTS: Expressions of PVT1 and MEG3 were higher in total migraineurs and both subgroups compared with controls (P < 0.0001). Meanwhile, expression of both lncRNA was higher in migraineurs with aura versus migraineurs without aura (P value < 0.0001 and = 0.01, respectively). Expression of DSCAM-AS1 was not different between any groups of patients compared with controls. Expression of LINC-ROR was elevated in total patients and patients with aura compared with controls (P value = 0.0002 and < 0.0001, respectively). It was also over-expressed in migraineurs with aura vs. migraineurs without aura (P = 0.01). Finally, expression of SPRY4-IT1 was higher in total patients and patients without aura compared with migraine-free persons (P values < 0.0001). Expressions of five mentioned lncRNAs were correlated in almost all study groups. In patients without aura, correlations were significant only for two pairs (SPRY4-IT1/PVT1 and SPRY4-IT1/DSCAM-AS1). PVT1 and MEG3 had the appropriate AUC, sensitivity and specificity values for separation of total migraineurs and both groups of patients from controls. The highest AUC value was reported for PVT1 in separation of migraineurs with aura from healthy controls (AUC = 0.98). CONCLUSION: Cumulatively, our study shows evidence for deregulation of lncRNAs in migraineurs.
Subject(s)
Migraine Disorders , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Female , Male , Adult , Middle Aged , Migraine Disorders/genetics , Migraine Disorders/metabolism , Migraine with Aura/geneticsABSTRACT
BACKGROUND: Cancer is the second leading cause of death in the world. Colorectal cancer is the third leading cause of cancer death. Today, there are several options for treating colorectal cancer such as chemotherapy, surgery, radiotherapy, immunotherapy, and gene therapy. 5-Fluorouracil is known as a suitable candidate for the treatment of various cancers, especially colorectal cancer. However, the use of this drug is limited, so it is usually used in combination with other drugs and agents. Based on the evidence obtained, this study attempted to evaluate the combined effects of 5-fluorouracil and caffeine on colorectal cancer cells. METHODS: In this study, initially HCT116 and HEK293 cell lines were cultured as cancer and normal cells, respectively. These cell lines were then evaluated for cytotoxicity, induction of apoptosis, and rate of cell migration. All data were analyzed by statistical methods. RESULTS: The results indicated that a combination of caffeine and 5-FU augmented their cytotoxicity in HCT116 cells but reduced cytotoxicity in HEK293 cells. No reduction was observed in the migration of HCT116 cells that were treated with caffeine or a combination of caffeine and 5-FU. Also, it seems that caffeine reverses the apoptotic effect of 5-FU in HCT116 cells.
Subject(s)
Apoptosis , Caffeine , Cell Movement , Cell Proliferation , Colorectal Neoplasms , Fluorouracil , Humans , Caffeine/pharmacology , Fluorouracil/pharmacology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Apoptosis/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , HEK293 Cells , HCT116 Cells , Tumor Cells, Cultured , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antimetabolites, Antineoplastic/pharmacologyABSTRACT
Cancer is a broad name for a group of diseases in which abnormal cells grow out of control and are characterized by their complexity and recurrence. Although there has been progress in cancer therapy with the entry of precision medicine and immunotherapy, cancer incidence rates have increased globally. Non-coding RNAs in the form of circular RNAs (circRNAs) play crucial roles in the pathogenesis, clinical diagnosis, and therapy of different diseases, including cancer. According to recent studies, circRNAs appear to serve as accurate indicators and therapeutic targets for cancer treatment. However, circRNAs are promising candidates for cutting-edge cancer therapy because of their distinctive circular structure, stability, and wide range of capabilities; many challenges persist that decrease the applications of circRNA-based cancer therapeutics. Here, we explore the roles of circRNAs as a replacement for cancer therapy, highlight the main challenges facing circRNA-based cancer therapies, and discuss the key strategies to overcome these challenges to improve advanced innovative therapies based on circRNAs with long-term health effects.
ABSTRACT
The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various sources, such as adipose tissue, bone marrow, peripheral blood, inner organs, and neonatal tissues. The regulation of inflammatory cytokines is crucial in inhibiting inflammatory diseases and promoting the presence of anti-inflammatory cytokines for infectious diseases. MSCs have been employed as therapeutic agents for tissue damage, diabetes, autoimmune diseases, and COVID-19 patients. Our research aimed to determine whether live or dead MSCs are more suitable for the treatment of COVID-19 patients. Our findings concluded that dead MSCs, when directly administered to the patient, offer advantages over viable MSCs due to their extended presence and higher levels of immune regulation, such as T-reg, B-reg, and IL-10, compared to live MSCs. Additionally, dead and apoptotic MSCs are likely to be more readily captured by monocytes and macrophages, prolonging their presence compared to live MSCs.
Subject(s)
COVID-19 , Communicable Diseases , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Infant, Newborn , Humans , SARS-CoV-2 , COVID-19 Vaccines , Cytokines , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic useABSTRACT
The DNA damage response (DDR) is a crucial cellular signaling pathway activated in response to DNA damage, including damage caused by chemotherapy. Chemoresistance, which refers to the resistance of cancer cells to the effects of chemotherapy, poses a significant challenge in cancer treatment. Understanding the relationship between DDR and chemoresistance is vital for devising strategies to overcome this resistance and improve treatment outcomes. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that do not code for proteins but play important roles in various biological processes, including cancer development and chemoresistance. RNA-binding proteins (RBPs) are a group of proteins that bind to RNA molecules and regulate their functions. The interaction between lncRNAs and RBPs has been found to regulate gene expression at the post-transcriptional level, thereby influencing various cellular processes, including DDR signaling pathways. Multiple studies have demonstrated that lncRNAs can interact with RBPs to modulate the expression of genes involved in cancer chemoresistance by impacting DDR signaling pathways. Conversely, RBPs can regulate the expression and function of lncRNAs involved in DDR. Exploring these interactions can provide valuable insights for the development of innovative therapeutic approaches to overcome chemoresistance in cancer patients. This review article aims to summarize recent research on the interaction between lncRNAs and RBPs during cancer chemotherapy, with a specific focus on DDR pathways.
Subject(s)
Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/metabolism , Drug Resistance, Neoplasm/genetics , Neoplasms/drug therapy , Neoplasms/genetics , DNA Damage/genetics , DNA Repair/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolismABSTRACT
KCNQ1OT1 is an lncRNA located within KCNQ1 gene on chromosome 11p15.5. This lncRNAs participates in the pathogenesis of a diversity of cancers as well as non-cancerous conditions. In most types of cancers, KCNQ1OT1 is regarded as an oncogene. In a wide array of cancers, high level of KCNQ1OT1 is associated with lower overall survival time. This lncRNA has been found to adsorb a variety of miRNAs, namely miR-15a, miR-211-5p, hsa-miR-107, miR-145, miR-34a, miR-204-5p, miR-129-5p, miR-372-3p, miR-491-5p, miR-153, miR-185-5p, miR-124-3p, miR-211-5p, miR-149, miR-148a-3p, miR-140-5p, miR-125b-5p, miR-9, miR-329-3p, miR-760, miR-296-5p, miR-3666 and miR-129-5p, thus regulating the downstream targets of these miRNAs. In this manuscript, our attention is on this lncRNA and its biomolecular roles in human cancers and other disorders. KCNQ1OT1 plays significant roles in the tumorigenesis and may function as a prospective target for cancer therapy.
Subject(s)
MicroRNAs , Neoplasms , RNA, Long Noncoding , Humans , MicroRNAs/genetics , Neoplasms/genetics , RNA, Long Noncoding/geneticsABSTRACT
Gastrointestinal cancers are a huge worldwide health concern, which includes a wide variety of digestive tract cancers. Circular RNAs (circRNAs), a kind of non-coding RNA (ncRNAs), are a family of single-stranded, covalently closed RNAs that have become recognized as crucial gene expression regulators, having an impact on several cellular functions in cancer biology. The gut microbiome, which consists of several different bacteria, actively contributes to the regulation of host immunity, inflammation, and metabolism. CircRNAs and the gut microbiome interact significantly to greatly affect the growth of GI cancer. Several studies focus on the complex functions of circRNAs and the gut microbiota in GI cancers, including esophageal cancer, colorectal cancer, gastric cancer, hepatocellular cancer, and pancreatic cancer. It also emphasizes how changed circRNA expression profiles and gut microbiota affect pathways connected to malignancy as well as how circRNAs affect hallmarks of gastrointestinal cancers. Furthermore, circRNAs and gut microbiota have been recommended as biological markers for therapeutic targets as well as diagnostic and prognostic purposes. Targeting circRNAs and the gut microbiota for the treatment of gastrointestinal cancers is also being continued to study. Despite significant initiatives, the connection between circRNAs and the gut microbiota and the emergence of gastrointestinal cancers remains poorly understood. In this study, we will go over the most recent studies to emphasize the key roles of circRNAs and gut microbiota in gastrointestinal cancer progression and therapeutic options. In order to create effective therapies and plan for the future gastrointestinal therapy, it is important to comprehend the functions and mechanisms of circRNAs and the gut microbiota.
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BACKGROUND: Alzheimer's disease (AD) is a multifaceted neurological ailment affecting more than 50 million individuals globally, distinguished by a deterioration in memory and cognitive abilities. Investigating neurotrophin growth factors could offer significant contributions to understanding AD progression and prospective therapeutic interventions. METHODS AND RESULTS: The present investigation collected blood samples from 50 patients diagnosed with AD and 50 healthy individuals serving as controls. The mRNA expression levels of neurotrophin growth factors and their receptors were measured using quantitative PCR. A Bayesian regression model was used in the research to assess the relationship between gene expression levels and demographic characteristics such as age and gender. The correlations between variables were analyzed using Spearman correlation coefficients, and the diagnostic potential was assessed using a Receiver Operating Characteristic curve. NTRK2, TrkA, TrkC, and BDNF expression levels were found to be considerably lower (p-value < 0.05) in the blood samples of AD patients compared to the control group. The expression of BDNF exhibited the most substantial decrease in comparison to other neurotrophin growth factors. Correlation analysis indicates a statistically significant positive association between the genes. The ROC analysis showed that BDNF exhibited the greatest Area Under the Curve (AUC) value of 0.76, accompanied by a sensitivity of 70% and specificity of 66%. TrkC, TrkA, and NTRK2 demonstrated considerable diagnostic potential in distinguishing between cases and controls. CONCLUSION: The observed decrease in the expression levels of NTRK2, TrkA, TrkC, and BDNF in AD patients, along with the identified associations between specific genes and their diagnostic capacity, indicate that these expressions have the potential to function as biomarkers for the diagnosis and treatment of AD.
Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Bayes Theorem , Brain-Derived Neurotrophic Factor/genetics , Receptor Protein-Tyrosine Kinases , BiomarkersABSTRACT
BACKGROUND: Calcium signaling has essential roles in the neurodevelopmental processes and pathophysiology of related disorders for instance autism spectrum disorder (ASD). METHODS AND RESULTS: We compared expression of SLC1A1, SLC25A12, RYR2 and ATP2B2, as well as related long non-coding RNAs, namely LINC01231, lnc-SLC25A12, lnc-MTR-1 and LINC00606 in the peripheral blood of patients with ASD with healthy children. Expression of SLC1A1 was lower in ASD samples compared with control samples (Expression ratio (95% CI) 0.24 (0.08-0.77), adjusted P value = 0.01). Contrary, expression of LINC01231 was higher in cases compared with control samples (Expression ratio (95% CI) 25.52 (4.19-154), adjusted P value = 0.0006) and in male cases compared with healthy males (Expression ratio (95% CI) 28.24 (1.91-418), adjusted P value = 0.0009). RYR2 was significantly over-expressed in ASD children compared with control samples (Expression ratio (95% CI) 4.5 (1.16-17.4), adjusted P value = 0.029). Then, we depicted ROC curves for SLC1A1, LINC01231, RYR2 and lnc-SLC25A12 transcripts showing diagnostic power of 0.68, 0.75, 0.67 and 0.59, respectively. CONCLUSION: To sum up, the current study displays possible role of calcium related genes and lncRNAs in the development of ASD.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , RNA, Long Noncoding , Child , Humans , Male , Calcium Signaling , Ryanodine Receptor Calcium Release ChannelABSTRACT
FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is a long non-coding RNA being transcribed from a locus on chromosome 1p33. This transcript has been found to be up-regulated in tumor samples of almost all types of malignancies in association with a significant increase in malignant features. FOXD2-AS1 can affect activity of PI3K/AKT, AKT/mTOR, Hippo/YAP, Notch, NRf2, Wnt/ß-catenin, NF-ÆB and ERK/MAPK pathways. Furthermore, it can enhance stem cell properties in cancer cells and prompt epithelial-mesenchymal transition. It is also involved in induction of resistance to a variety of anticancer agents such as adriamycin, cisplatin, 5-fluorouracil, temozolomide and gemcitabine. This article summarizes the impact of FOXD2-AS1 in diverse human disorders.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Humans , Cell Line, Tumor , Cell Proliferation/genetics , Cisplatin , Gemcitabine , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
Schimke immuno-osseous dysplasia (SIOD) is a rare multi-system condition caused by biallelic loss-of-function mutations in the SMARCAL1 gene. This disorder is characterized by disproportionate growth failure, T-cell deficiency, and renal dysfunction. Pathogenic variants in the SMARCAL1 gene have been reported in only approximately half of SIOD-affected individuals. Among these alterations, nonsense and frameshift mutations generally lead to a severe phenotype with early onset. In this study, we identified novel mutations in an Iranian patient with SIOD. A 4-year-old girl with developmental delay and facial dysmorphism was referred to our center for molecular diagnosis. We applied whole-exome and Sanger sequencing for co-segregation analysis. Subsequently, bioinformatic analysis was performed to assess the pathogenic effects of the variants and their post-transcriptional effects. We discovered two novel mutations (c.2281delT and c.2283delA) in exon 15 of the SMARCAL1 gene, resulting in a truncated protein with a loss of 193 amino acids (p.S761Rfs*1). Variant effect predictors indicated that these variants are pathogenic, and multi-sequence alignments revealed high conservation of this region among different species. Given that our patient exhibited severe a phenotype and passed away soon after receiving a definitive molecular diagnosis, we propose that the loss of the helicase C-terminal domain in the deleted part of SMARCAL1 may lead to the severe form of SIOD. Besides, the combination of growth retardation and bone abnormalities also plays a crucial role in the early diagnosis of the disease.
Subject(s)
Arteriosclerosis , Immunologic Deficiency Syndromes , Nephrotic Syndrome , Osteochondrodysplasias , Primary Immunodeficiency Diseases , Pulmonary Embolism , Female , Humans , Child, Preschool , Iran , Primary Immunodeficiency Diseases/genetics , Primary Immunodeficiency Diseases/complications , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/metabolism , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/genetics , Nephrotic Syndrome/complications , DNA Helicases/geneticsABSTRACT
Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies (AU)
Subject(s)
Humans , Carcinogenesis/genetics , Carcinogenesis/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Esophageal Neoplasms/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, NeoplasticABSTRACT
Obesity is a worldwide health problem with an increasing trend. This condition has a significant genetic background. H19 lncRNA has been shown to protect from dietary obesity through decreasing levels of monoallelic genes in brown fat. In the current study, we aimed to find the association between two possibly functional H19 polymorphisms, namely rs217727 and rs2839698 and obesity in Iranian population. These polymorphisms have been shown to affect risk of some obesity-related conditions in different populations. The study included 414 obese cases and 392 controls. Notably, both rs2839698 and rs217727 were associated with obesity in the allelic model as well as all supposed inheritance models. In addition, after adjustment for gender, all P values remained significant. For rs2839698, the OR (95% CI) for T allele vs. C allele was 3.29 (2.67-4.05) (P-value < 0.0001). In the co-dominant model, both TT and CT genotypes were found to confer risk of obesity compared with CC genotype (OR (95% CI)= 14.02 (8.39-23.43) and 9.45 (6.36-14.04), respectively). Similarly, combination of TT and CT genotypes had an OR (95% CI) = 10.32 (7.03-15.17) when compared with CC genotype. For rs217727, the T allele was found to exert a protective effect (OR (95% CI) = 0.6 (0.48-0.75)). Moreover, in the co-dominant model, OR (95% CI) values for TT and TC genotypes vs. CC genotype were 0.23 (0.11-0.46) and 0.65 (0.49-0.87), respectively. Taken together, H19 polymorphisms may affect risk of obesity in Iranian population. It is necessary to conduct functional studies to confirm a causal relationship between the rs217727 and rs2839698 polymorphisms and obesity.