The oxidative stress-associated long non-coding RNAs in pancreatic cancer.

PURPOSE: A lot of people are dying from pancreatic cancer (PC) annually. The early detection of this cancer is particularly challenging due to the fact that symptoms tend to appear in advanced stages. It has been suggested that oxidative stress may play a role in the development of PC. Several genes regulate this process, including long noncoding RNAs (lncRNAs). There is no comprehensive study on the expression pattern of lncRNAs related to oxidative stress in PC patients. In the present case-control study, we quantified levels of oxidative stress-associated lncRNAs in PC patients versus healthy controls. PATIENTS AND METHODS: In the present study, we investigated the expression levels of lincRNA-p21, LUCAT, RMST, FOXD3-AS1, and MT1DP lncRNAs in the peripheral blood mononuclear cells (PBMCs) of 53 â€‹PC patients and 50 healthy controls. The association between lncRNA expression and clinical and pathological characteristics was also evaluated. RESULTS: The expression of lincRNA-P21 and rhabdomyosarcoma 2-associated transcript (RMST) lncRNAs in PC patients has significantly decreased. Expression of lncRNA RMST was significantly higher in TNM stage III-IV patients in comparison to TNM stage I-II patients. In addition, a significant positive association was recognized between candidate lncRNA expression, and finally, the AUC values of the expression levels of lincRNA-p21 and RMST were 0.60 and 0.61, respectively. CONCLUSIONS: Altogether, our study suggests a possible role of lincRNA-p21 and RMST lncRNAs in the etiology of PC pathobiology, and their biomarker role may be understood in future studies.

Noncoding RNAs in B cell non-Hodgkins lymphoma.

B-cell non-Hodgkins lymphomas (BCNHLs) are a category of B-cell cancers that show heterogeneity. These blood disorders are derived from different levels of B-cell maturity. Among NHL cases, ∼80-90 % are derived from B-cells. Recent studies have demonstrated that noncoding RNAs (ncRNAs) contribute to almost all parts of mechanisms and are essential in tumorigenesis, including B-cell non-Hodgkins lymphomas. The study of ncRNA dysregulations in B-cell lymphoma unravels important mysteries in lymphoma's molecular etiology. It seems also necessary for discovering novel trials as well as investigating the potential of ncRNAs as markers for their diagnosis and prognosis. In the current study, we summarize the role of ncRNAs involving miRNAs, long noncoding RNAs, as well as circular RNAs in the development or progression of BCNHLs.

The Expression Analysis of Long Non-coding RNAs Related to Wnt/ß-Catenin Signaling in Pancreatic Cancer Patients.

Background The oncogenic Wnt/ß-catenin signaling plays a critical role in carcinogenesis, prognosis, and resistance to therapy. Pancreatic cancer (PC) has high mortality because of its poor prognosis. Several studies have suggested that lncRNAs are directly involved in the development and progression of PC as well as in Wnt/ß-catenin signaling. In this study, we investigated and compared the expression of Wnt/ß-catenin signaling-related ZFAS1 and HCG11 lncRNAs, and their targets, CTNNB1 and IGF2BP1 genes in the blood of patients with PC and healthy individuals. A total of 47 PC patients and 50 healthy individuals participated in this study. RNA was extracted from the peripheral blood samples of participants, and cDNA was synthesized. The expression level of the selected genes was quantified by real-time PCR. The expression of HCG11 lncRNA and CTNNB1 genes in patients with PC was significantly upregulated compared to healthy individuals, and the expression of the ZFAS1 lncRNA was significantly downregulated. According to the analysis of the ROC curve, the diagnostic powers of ZFAS1 and CTNNB1 in PC were 0.67 and 0.69, respectively. Altogether, the present study suggests a role for ZFAS1 and HCG11 lncRNAs and CTNNB1 and IGF2BP1 in the pathogenesis of pancreatic cancer. Moreover, the peripheral expression of these lncRNAs may be useful as potential biomarkers for PC.

A review on the role of KCNQ1OT1 lncRNA in human disorders.

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.

Neurotrophin growth factors and their receptors as promising blood biomarkers for Alzheimer's Disease: a gene expression analysis study.

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.

Abnormal expression of long non-coding RNAs RMRP, CTC-487M23.5, and DGCR5 in the peripheral blood of patients with Bipolar disorder.

Long non-coding RNAs (lncRNAs) have been recently considered as one of the regulatory mechanisms of the nervous system. Hence, lncRNAs may be considered diagnostic biomarkers for bipolar disorder (BD). We aimed to investigate the expression of RMRP, CTC-487M23.5, and DGCR5 lncRNAs in bipolar patients. The levels of these three lncRNAs were measured in peripheral blood mononuclear cells (PBMCs) of 50 BD patients and 50 healthy subjects by real-time PCR. Moreover, we performed a ROC curve analysis between the gene expression and some clinical features of BD patients. Significant upregulation of RMRP and CTC-487M23.5 and no significant change in levels of DGCR5 was observed in BD individuals compared with controls. Also, we found upregulation of RMRP and downregulation of CTC-487M23.5 and DGCR5 in females with BD. The areas under the ROC curve (AUC) for RMRP and CTC-487M23.5 lncRNAs were 0.80 and 0.61, respectively. There was no significant correlation between the expression of these three lncRNAs and clinical features in PBMCs of BD patients. These results suggest a role for RMRP and CTC-487M23.5 in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these two lncRNAs might be beneficial as potential biomarkers for BD.

hTERT Gene Modification Using CRISPR-dCas9-dnmt3a System as a Therapeutic Approach Against Glioma.

Background: Abnormal DNA methylation patterns have been reported in various diseases, including different cancers. CRISPR/Cas9 is a low-cost and highly effective gene editing tool that has lately revolutionized biotechnology. Studies have shown that the CRISPR/Cas9 system can effectively target and correct methylation. Objectives: Telomerase plays a survival role for cancer cells. It is encoded by the hTERT gene. The effectiveness of CRISPR/Cas9 in targeting hTERT to treat glioma cancer cells was assessed in this study. Methods: EF1a-hsaCas9-U6-gRNA vector carrying sgRNA and Cas9 hybrids were used to transfect U87 glioma cells. Four and eight µg/mL polybrene concentrations were investigated to improve transfection efficiency. The expression level of hTERT that has undergone metabisulfite modification was assessed using real-time PCR. Flow cytometry and Western blotting were also used to determine whether telomerase was present in the cells. High-resolution melting analysis (HRM) was used to examine the hTERT promoter's methylation. Finally, flow cytometry was used to measure the apoptotic rate of transfected U87 cells. Results: The findings demonstrated that gRNA significantly boosted transfection effectiveness. Significant variations were seen in the expression of hTERT in U87 cells at 4 µg/mL polybrene and 80 µg/mL transfection compared to transfection without gRNA and basal cells. Flow cytometry showed a decrease in hTERT levels in transfected cells. Furthermore, transfection with gRNA increased U87 cell apoptosis compared to transfection without gRNA. Conclusions: It appears that the designed CRISPR/Cas9 system can reduce hTERT expression and telomerase activity and thus inhibit glioma cell growth.

Expression analysis of inhibitory B7 family members in Alzheimer's disease.

Alzheimer's disease (AD) is a global health problem due to its complexity, which frequently makes the development of treatment methods extremely difficult. Therefore, new methodologies are necessary to investigate the pathophysiology of AD and to treat AD. The interaction of immune modulation and neurodegeneration has added new dimensions in current knowledge of AD etiology and offers an attractive opportunity for the discovery of novel biomarkers and therapies. Using quantitative polymerase chain reaction, we compared the expression levels of inhibitory B7 family members (B7-1, B7-2, B7-H1, B7-DC, B7-H3, B7-H4, B7-H5, B7-H7, and ILDR2), as immune regulators, in the peripheral blood of late-onset AD (LOAD) patients (n = 50) and healthy individuals (n = 50). The levels of B7-2, B7-H4, ILDR2, and B7-DC expression were significantly higher in-patient blood samples than in control blood samples. Furthermore, we discovered a substantial positive correlation between all gene expression levels. In addition, the current study indicated that ILDR2, B7-H4, B7-2, and B7-DC might serve as diagnostic biomarkers to identify LOAD patients from healthy persons. The present work provides additional evidence for the significance of inhibitory B7 family members to the etiology of LOAD.

Reduction of GAS5 and FOXD3-AS1 long non-coding RNAs in patients with bipolar disorder.

Bipolar disorder (BD) patients suffer from severe disability and premature death because of failure in prognosis, diagnosis, and treatment. Although neural mechanisms of bipolar have not been fully discovered, studies have shown long noncoding RNAs (lncRNAs) can play an important role in signaling pathways such as PI3K/AKT pathway. There has been little study on deregulated lncRNAs and the lncRNAs' mode of action in the BD. Hence, we aimed to investigate the expression of PI3K/AKT pathway-related lncRNAs named TUG1, GAS5, and FOXD3-AS1 lncRNAs in the PMBC in 50 bipolar patients and 50 healthy controls. Our results showed that FOXD3-AS1 and GAS5 under-expressed significantly in bipolar patients compared to healthy controls (P = 0.0028 and P < 0.0001 respectively). Moreover, after adjustment, all P values remained significant (q value < 0.0001). According to the ROC curve, AUC (area under the curve), specificity, and sensitivity of these lncRNAs, GAS5 and FOXD3-AS1 might work as BD candidate diagnostic biomarkers. Taken together, the current results highlight that the dysregulation of FOXD3-AS1 and GAS5 may be associated with an increased risk of BD.

Deregulation of NF-κB associated long non-coding RNAs in bipolar disorder.

Long non-coding RNAs (lncRNAs) are major genetic factors whose disruption lead to many diseases, including nervous system diseases. Bipolar disorder (BD) is a neuro-psychiatric disease with no definitive diagnosis and incomplete treatment. Regarding the role of NF-κB-associated lncRNAs in the neuro-psychiatric disorders, we examined the expression of three lncRNAs, DICER1-AS1, DILC, and CHAST, in BD patients. To assess lncRNA expression in peripheral blood mononuclear cells (PBMCs) of 50 BD patients and 50 healthy individuals, Real-time PCR was used. Additionally, some clinical characteristics of BD patients were investigated via an analysis of ROC curves and correlations. Based on our results, the expression level of CHAST increased significantly in BD patients in comparison with healthy people, in BD men compared with healthy men, as well as in BD women in comparison with control females (p < 0.05). A similar increase in expression was observed for DILC and DICER1-AS1 lncRNAs in female patients compared with healthy women. Whereas compared to healthy men, DILC was decreased in diseased men. Based on the results of the ROC curve, the area under the curve (AUC) for CHAST lncRNA was 0.83 with a P value of 0.0001. So, the expression level of CHAST lncRNA could play a role in the pathobiology of the BD and be considered a good putative biomarker for individuals with bipolar disorder.

A gene expression analysis of long non-coding RNAs NKILA and PACER as well as their target genes, NF-κB and cox-2 in bipolar disorder patients.

Bipolar disorder (BD) is a severe condition characterized by periods of mania and depression. Despite advances in the neurobiology of bipolar disorder, the exact etiology of the disease remains unclear. There is evidence that Inflammation is associated with bipolar disorder. COX-2 and NF-κB are two critical mediators in the inflammatory pathways. Long non-coding RNAs (lncRNAs) are a new class of non-coding RNAs that play a wide range of roles, especially in developing and maintaining normal brain functions. Two lncRNAs called PACER and NKILA control the expression of COX-2 and NF-κB genes, respectively. In this study, Expression levels of PACER and NKILA lncRNAs, as well as, COX-2 and NF-κB genes were measured in fifty patients with bipolar disorder and 50 healthy individuals by real-time PCR. Expression levels of NKILA and COX2 were considerably reduced in BD patients compared with healthy controls. Such significant downregulation in the expression of NKILA and PACER was only observed in male patients with BD compared with male healthy subjects. Also, according to the results of the ROC curve, the area under curve values for NKILA and COX2 were 0.68 and 0.52 respectively. Consequently, the NKILA gene could be considered a biomarker. By examining the degree of pairwise correlation between genes, all genes had a significant positive correlation with each other. Taken together, these results revealed a function for NKILA and PACER lncRNAs in the pathogenesis of BD.

The key roles of non-coding RNAs in the pathophysiology of hypertension.

Hypertension is a multifactorial condition in which several genetic and environmental elements contribute. Recent investigations have revealed contribution of non-coding region of the transcriptome in this trait. CDKN2B-AS1, AK098656, MEG3, H19, PAXIP1-AS1, TUG1, GAS5, CASC2 and CPS1-IT are among long non-coding RNAs participating in the pathophysiology of hypertension. Several miRNAs have also been found to be implicated in this disorder. miR-296, miR-637, miR-296, miR-637, hsa-miR-361-5p, miR-122-5p, miR-199a-3p, miR-208a-3p, miR-423-5p, miR-223-5p and miR-140-5p are among dysregulated miRNAs in this condition whose application as diagnostic biomarkers for hypertension has been evaluated. Finally, hsa-circ-0005870, hsa_circ_0037911 and hsa_circ_0014243 are examples of dysregulated circular RNAs in hypertensive patients. In the current review, we describe the role of these non-coding RNAs in the pathophysiology of hypertension.

Downregulation of long non-coding RNAs in patients with bipolar disorder.

The abnormal function of signaling cascades is currently a candidate in the pathophysiology of bipolar disorder (BD). One of the factors involved in activating these signals is oxidative stress. Some long non-coding RNAs (lncRNA) are involved in the oxidative stress. In this study, we compared expression levels of lincRNA-p21, lincRNA-ROR, and lincRNA-PINT in the peripheral blood mononuclear cells (PBMC) from BD patients (n = 50) and healthy individuals (n = 50). Expression levels of lincRNA-p21, lincRNA-ROR, and lincRNA-PINT were significantly reduced in patients with BD compared to controls. In sex-based analyses, down-regulation of these lncRNAs was revealed only in male BD patients compared to male healthy subjects. Also, in BD patients, all three lncRNAs showed a significant pairwise positive correlation in expression level. The area under curve values for lincRNA-p21, lincRNA-ROR, and lincRNA-PINT was 0.66, 0.75, and 0.66, respectively. Thus, the ROC curve analysis showed that lncRNA-ROR might serve as a diagnostic biomarker for distinguishing between BD patients and controls. Altogether, the current study proposes a role for lincRNA-p21, lincRNA-ROR, and lincRNA-PINT in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these lncRNAs might be useful as potential biomarkers for BD.

Significant reduction of long non-coding RNAs expression in bipolar disorder.

Long non-coding RNAs (lncRNAs) have been recently emerged as critical modulators of oxidative stress pathway. Likewise, rising evidence currently highlights dysfunction of oxidative stress pathways in bipolar disorder (BD) patients.In the current study, we evaluated the expression levels of H19, SCAL1 (LUCAT1), RMST, MEG3 and MT1DP lncRNAs in the PBMC from 50 patients with BD and 50 control subjects (male/female ratio in each group: 70%/30%). Expression levels of SCAL1, RMST and MEG3 but not H19 and MT1DP were considerably decreased in BD patients compared with healthy individuals. Such significant decrease in the expression of MEG3, RMST and SCAL1 was only reported in male BD patients compared with male controls. Substantial pairwise correlations were observed between expression levels of these lncRNAs in BD subjects. The area under curve values for RMST, MEG3 and SCAL1 were 0.70, 0.63 and 0.61 respectively. On the basis of this finding, RMST had the best efficiency in the discrimination of disease status between BD patients and controls. Taken together, the current results suggest a role for MEG3, RMST and SCAL1 lncRNAs in the pathogenesis of BD. In addition, peripheral expression levels of these lncRNAs might serve as potential peripheral markers for BD.

The Emerging Role of EMT-related lncRNAs in Therapy Resistance and their Applications as Biomarkers.

Cancer is the world's second-largest cause of death. The most common cancer treatments are surgery, radiation therapy, and chemotherapy. Drug resistance, epithelial-- to-mesenchymal transition (EMT), and metastasis are pressing issues in cancer therapy today. Increasing evidence showed that drug resistance and EMT are co-related with each other. Indeed, drug-resistant cancer cells possess enhanced EMT and invasive ability. Recent research has demonstrated that lncRNAs (long non-coding RNAs) are non-coding transcripts which play an important role in the regulation of EMT, metastasis, and drug resistance in different cancers. However, the relationships among lncRNAs, EMT, and drug resistance are still unclear. These effects could be exerted via several signaling pathways, such as TGF-ß, PI3K-AKT, and Wnt/ß-catenin. Identifying the crucial regulatory roles of lncRNAs in these pathways and processes leads to the development of novel targeted therapies. We review the key aspects of lncRNAs associated with EMT and therapy resistance. We focus on the crosstalk between lncRNAs and molecular signaling pathways affecting EMT and drug resistance. Moreover, each of the mentioned lncRNAs could be used as a potential diagnostic, prognostic, and therapeutic therapy resistancefor cancer. However, the investigation of lncRNAs for clinical applications still has several challenges.

Emerging role of non-coding RNAs in the regulation of KRAS.

The Kirsten ras oncogene KRAS is a member of the small GTPase superfamily participating in the RAS/MAPK pathway. A single amino acid substitution in KRAS gene has been shown to activate the encoded protein resulting in cell transformation. This oncogene is involved in the malignant transformation in several tissues. Notably, numerous non-coding RNAs have been found to interact with KRAS protein. Such interaction results in a wide array of human disorders, particularly cancers. Orilnc1, KIMAT1, SLCO4A1-AS1, LINC01420, KRAS1P, YWHAE, PART1, MALAT1, PCAT-1, lncRNA-NUTF2P3-001 and TP53TG1 are long non-coding RNAs (lncRNAs) whose interactions with KRAS have been verified in the context of cancer. miR-143, miR-96, miR-134 and miR-126 have also been shown to interact with KRAS in different tissues. Finally, circITGA7, circ_GLG1, circFNTA and circ-MEMO1 are examples of circular RNAs (circRNAs) that interact with KRAS. In this review, we describe the interaction between KRAS and lncRNAs, miRNAs and circRNAs, particularly in the context of cancer.

Emerging Impact of Non-coding RNAs in the Pathology of Stroke.

Ischemic stroke (IS) is an acute cerebral vascular event with high mortality and morbidity. Though the precise pathophysiologic routes leading to this condition are not entirely clarified, growing evidence from animal and human experiments has exhibited the impact of non-coding RNAs in the pathogenesis of IS. Various lncRNAs namely MALAT1, linc-SLC22A2, linc-OBP2B-1, linc_luo_1172, linc-DHFRL1-4, SNHG15, linc-FAM98A-3, H19, MEG3, ANRIL, MIAT, and GAS5 are possibly involved in the pathogenesis of IS. Meanwhile, lots of miRNAs contribute in this process. Differential expression of lncRNAs and miRNAs in the sera of IS patients versus unaffected individuals has endowed these transcripts the aptitude to distinguish at risk patients. Despite conduction of comprehensive assays for evaluation of the influence of lncRNAs/miRNAs in the pathogenesis of IS, therapeutic impacts of these transcripts in IS have not been clarified. In the present paper, we review the impact of lncRNAs/miRNAs in the pathobiology of IS through assessment of evidence provided by human and animal studies.

DNA methylation signature as a biomarker of major neuropsychiatric disorders.

DNA methylation is a broadly-investigated epigenetic modification that has been considered as a heritable and reversible change. Previous findings have indicated that DNA methylation regulates gene expression in the central nervous system (CNS). Also, disturbance of DNA methylation patterns has been associated with destructive consequences that lead to human brain diseases such as neuropsychiatric disorders (NPDs). In this review, we comprehensively discuss the mechanism and function of DNA methylation and its most recent associations with the pathology of NPDs-including major depressive disorder (MDD), schizophrenia (SZ), autism spectrum disorder (ASD), bipolar disorder (BD), and attention/deficit hyperactivity disorder (ADHD). We also discuss how heterogeneous findings demand further investigations. Finally, based on the recent studies we conclude that DNA methylation status may have implications in clinical diagnostics and therapeutics as a potential epigenetic biomarker of NPDs.

Prediction of Single-Nucleotide Polymorphisms within microRNAs Binding Sites of Neuronal Genes Related to Multiple Sclerosis: A Preliminary Study.

BACKGROUND: Different genetic variants, including the single-nucleotide polymorphisms (SNPs) present in microRNA recognition elements (MREs) within 3'UTR of genes, can affect miRNA-mediated gene regulation and susceptibility to a variety of human diseases such as multiple sclerosis (MS), a disease of the central nervous system. Since the expression of many genes associated with MS is controlled by microRNAs (miRNAs), the aim of this study was to analyze SNPs within miRNA binding sites of some neuronal genes associated with MS. MATERIALS AND METHODS: Fifty-seven neuronal genes related to MS were achieved using dbGaP, DAVID, DisGeNET, and Oviddatabases. 3'UTR of candidate genes were assessed for SNPs, and miRNAs' target prediction databases were used for predicting miRNA binding sites. RESULTS: Three hundred and eight SNPs (minor allele frequency >0.05) were identified in miRNA binding sites of 3'UTR of 44 genes. Among them, 42 SNPs in 22 genes had miRNA binding sites and miRNA prediction tools suggested 71 putative miRNAs binding sites on these genes. Moreover, in silico analysis predicted 22 MRE-modulating SNPs and 22 MRE-creating SNPs in the 3'UTR of these candidate genes. CONCLUSIONS: These candidate MRE-SNPs can alter miRNAs binding sites and mRNA gene regulation. Therefore, these genetic variants and miRNAs might be involved in MS susceptibility and pathogenesis and hence would be valuable for further functional verification investigation.

Vitamin D changes expression of DNA repair genes in the patients with multiple sclerosis.

Oxidative stress (OS) plays an essential role in demyelination and tissue injury related to pathogenesis of multiple sclerosis (MS). On the other hand, vitamin D (VD) as an antioxidant reduces oxidative stress and has been used as adjuvant therapy in autoimmune diseases. Although VD supplementation is suggested as a protective and immunomodulation factor for MS patients, the molecular mechanisms remain unclear. Given that VD may modulate the immune system of MS patients through the DNA repair pathway, we aimed to evaluate the effects of VD supplementation in DNA repair genes expression including OGG1, MYH, MTH1, and ITPA. Transcript levels were measured using the RT-qPCR method in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) patients before and after two months of VD supplementation. Furthermore, in silico analysis and correlation gene expression analysis was performed to find the biological binding sites and the effect of NRF2 on the regulation of DNA repair genes. Our data revealed that in MS patients, 2-month VD treatment significantly altered the expression of MYH, OGG1, MTH1, and NRF2 genes. A significant correlation was observed between DNA repair genes and NRF2 expression, which was confirmed by the presence of antioxidant response element (ARE) binding sites in the promoter of OGG1, MYH, and MTH1 genes. This study demonstrated that the impact of VD on MS patients may be mediated through the improvement of DNA repair system efficiency. This finding brought some new evidence for the involvement of DNA repair genes in the physiopathology of MS patients.