scholarly journals Long Non-Coding RNA H19 Expression and Functional Polymorphism rs217727 Are Linked to Increased Ischemic Stroke Risk

Author(s):  
Mohadese Rezaei ◽  
Mohammad Javad Mokhtari ◽  
Mahnaz Bayat ◽  
Anahid Safari ◽  
Mehdi Dianatpuor ◽  
...  

Abstract Background: Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing the prevalence of IS risk factors. We evaluated the correlation between H19 rs217727 polymorphism and the expression level of H19 lncRNA with susceptibility to IS among the Iranian population.Methods: Blood samples were collected from IS patients (n = 114) and controls (n = 114). We concentrated on the expression pattern of H19 at different time points (i.e., 0-24, 24-48, and 48-72 hours after stroke). The tetra-primer ARMS-PCR method was applied for DNA genotyping. We used the quantitative real-time PCR to evaluate H19 expression levels. Results: The rs217727polymorphism of H19 was related with IS susceptibility in the co-dominant (OR=2.92, 95% CI=0.91-10.92, P=0.04) and recessive models (OR=2.80, 95% CI=0.96-8.15, P=0.04). H19 expression was significantly upregulated in IS and remained high for 72 hours after stroke. ROC curves showed that H19 expression within the first 24 hours from stroke onset might serve as a biomarker for the early diagnosis of IS with 79.49% sensitivity and 80.00% specificity. H19 expression in SVO and LAA patients were 3.74 and 3.34 times higher than the UD subtype, respectively [OR=3.74 95% CL (1.14-12.27) P=0.030 and OR=3.34 95% CL (1.13-9.85) P=0.029].Conclusion: The rs217727 polymorphism of the H19 is correlated with IS susceptibility, and H19 expression levels were higher in SVO and LAA patients. The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population.

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mohadese Rezaei ◽  
Mohammad Javad Mokhtari ◽  
Mahnaz Bayat ◽  
Anahid Safari ◽  
Mehdi Dianatpuor ◽  
...  

Abstract Background Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing the prevalence of IS risk factors. We evaluated the correlation between H19 rs217727 polymorphism and the expression level of H19 lncRNA with susceptibility to IS among the Iranian population. Methods Blood samples were collected from IS patients (n = 114) and controls (n = 114). We concentrated on the expression pattern of H19 at different time points (i.e., 0–24, 24–48, and 48–72 h after stroke). The tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method was applied for DNA genotyping. We used the quantitative real-time PCR to evaluate H19 expression levels. We used the receiver operating characteristic (ROC) curve to evaluate the diagnosis and prognosis of IS. Results The rs217727polymorphism of H19 was related with IS susceptibility in the co-dominant (OR = 2.92, 95% CI = 0.91–10.92, P = 0.04) and recessive models (OR = 2.80, 95% CI = 0.96–8.15, P = 0.04). H19 expression was significantly upregulated in IS and remained high for 72 h after stroke. ROC curves showed that H19 expression within the first 24 h from stroke onset might serve as a biomarker for the early diagnosis of IS with 79.49% sensitivity and 80.00% specificity. H19 expression in small vessel occlusion (SVO) and large-artery atherosclerosis (LAA) patients were 3.74 and 3.34 times higher than the undetermined (UD) subtype, respectively [OR = 3.74 95% CL (1.14–12.27) P = 0.030 and OR = 3.34 95% CL (1.13–9.85) P = 0.029]. Conclusion The rs217727 polymorphism of the H19 is correlated with IS susceptibility, and H19 expression levels were higher in SVO and LAA patients. The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population, but it cannot serve as a useful prognostic marker.


Author(s):  
Yanbing Li ◽  
Yu Geng ◽  
Boda Zhou ◽  
Xuejiao Wu ◽  
Ou Zhang ◽  
...  

AbstractIt is formerly conducted that long non-coding RNA growth arrest-specific 5 (GAS5) is involved in the process of coronary atherosclerosis (AS). The regulatory effects of GAS5 on the microRNA (miR)-194-3p/thioredoxin-interacting protein (TXNIP) axis in AS have been insufficiently explored yet. Thereafter, this work is started from GAS5/miR-194-3p/TXNIP axis in AS. AS rats were modeled to obtain their coronary vascular tissues and endothelial cells (ECs), in which GAS5, miR-194-3p, and TXNIP expression were tested. ECs were identified by immunohistochemistry. The mechanism among GAS5, miR-194-3p, and TXNIP was determined. ECs were transfected with inhibited GAS5 or overexpressed miR-194-3p to decipher their functions in proliferation and apoptosis of ECs in AS. Raised GAS5 and TXNIP and degraded miR-194-3p expression levels exhibited in AS. GAS5 bound to miR-194-3p while miR-194-3p targeted TXNIP. Depleting GAS5 or restoring miR-194-3p enhanced proliferation and depressed apoptosis of ECs in AS. This work clearly manifests that inhibited GAS5 facilitates the growth of ECs through miR-194-3p-targeted TXNIP in AS, consolidating the basal reference to the curing for AS.


2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Xuefang Liu ◽  
Xinliang Ming ◽  
Wei Jing ◽  
Ping Luo ◽  
Nandi Li ◽  
...  

Increasing studies are indicating that long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is associated with the prognosis of cancer patients. However, the results have been disputed. Therefore, we aimed to further explore the prognostic value and clinical significance of XIST in various types of cancers. Then, we focussed our research on the comparison of the predictive value of XIST between digestive system tumors and non-digestive system tumors. We performed a systematic search by looking up PubMed, Embase, Cochrane Library, Web of Science, and Medline (up to 3 January 2018). Fifteen studies which matched our inclusion criteria with a total of 920 patients for overall survival and 867 patients for clinicopathological characteristics were included in this meta-analysis. Pooled hazard ratios (HR) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were calculated to summarize the effects. Our results suggested that high expression levels of XIST were associated with unfavorable overall survival in cancer patients (pooled HR = 1.81, 95% CI: 1.45–2.26). Additionally, we found that XIST was more valuable in digestive system tumors (pooled HR = 2.24, 95% CI: 1.73–2.92) than in non-digestive system tumors (pooled HR = 1.22, 95% CI: 0.60–2.45). Furthermore, elevated expression levels of XIST were connected with distant metastasis and tumor stage. XIST was correlated with poor prognosis, which suggested that XIST might serve as a novel predictive biomarker for cancer patients, especially for patients of digestive system tumors.


Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 506 ◽  
Author(s):  
Edie-Rosmin Wu ◽  
Ying-Erh Chou ◽  
Yu-Fan Liu ◽  
Kuan-Chun Hsueh ◽  
Hsiang-Lin Lee ◽  
...  

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, whose diversified occurrence worldwide indicates a connection between genetic variations among individuals and the predisposition to such neoplasms. Mounting evidence has demonstrated that long non-coding RNA (lncRNA) H19 can have both promotive and inhibitory effects on cancer development, revealing a dual role in tumorigenesis. In this study, the link of H19 gene polymorphisms to hepatocarcinogenesis was assessed between 359 HCC patients and 1190 cancer-free subjects. We found that heterozygotes for the minor allele of H19 rs2839698 (T) and rs3741219 (G) were more inclined to develop HCC (OR, 1.291; 95% CI, 1.003–1.661; p = 0.047, and OR, 1.361; 95% CI, 1.054–1.758; p = 0.018, respectively), whereas homozygotes for the polymorphic allele of rs2107425 (TT) were correlated with a decreased risk of HCC (OR, 0.606; 95% CI, 0.410–0.895; p = 0.012). Moreover, patients who bear at least one variant allele (heterozygote or homozygote) of rs3024270 were less prone to develop late-stage tumors (for stage III/IV; OR, 0.566; 95% CI, 0.342–0.937; p = 0.027). In addition, carriers of a particular haplotype of three H19 SNPs tested were more susceptible to HCC. In conclusion, our results indicate an association between H19 gene polymorphisms and the incidence and progression of liver cancer.


2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093429 ◽  
Author(s):  
Hui Zhou ◽  
Weifeng Shen ◽  
Hongxing Zou ◽  
Qingshan Lv ◽  
Pingyang Shao

Objective Long non-coding RNAs (lncRNAs) are involved in carcinogenesis and could be used as diagnostic biomarkers. Our study aimed to elucidate the clinical role of serum exosomal lncRNA H19 in gastric cancer (GC). Methods In this prospective clinical study, we determined serum exosomal lncRNA H19 levels in 81 patients with GC and analysed the correlations between serum lncRNA H19 levels and clinical characteristics. Receiver operating characteristics (ROC) curves were constructed to determine the diagnostic performance of exosomal lncRNA H19 in GC. Results Serum exosomal lncRNA H19 levels were significantly upregulated in patients with GC both before and after surgery compared with healthy controls. Furthermore, serum exosomal lncRNA H19 levels were significantly decreased after compared with before surgery in patients with GC. Preoperative lncRNA H19 levels were significantly correlated with TNM stage. The area under the ROC curve (AUC) value for exosomal lncRNA H19 was 0.849, which was significantly higher than the AUC values for cancer antigens 19-9 and 72-4 and carcinoembryonic antigen, either alone or combined. Conclusions These results suggest that circulating exosomal lncRNA H19 may be a potential biomarker with diagnostic and prognostic value in GC.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3086
Author(s):  
Cong Zhou ◽  
Shiwei Duan

Studies have shown that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), play an important regulatory role in the occurrence and development of human cancer. Nicotinamide nucleotide transhydrogenase-antisense 1 (NNT-AS1) is a newly-discovered cytoplasmic lncRNA. Many studies have shown that it has abnormally-high expression levels in malignant tumors, but there are also a few studies that have reported low expression levels of NNT-AS1 in gastric cancer, breast cancer, and ovarian cancer. At present, the regulatory mechanism of NNT-AS1 as a miRNA sponge, which may be an important reason affecting tumor cell proliferation, invasion, metastasis, and apoptosis is being studied in-depth. In addition, NNT-AS1 has been found to be related to cisplatin resistance. In this review, we summarize the abnormal expression of NNT-AS1 in a variety of neoplastic diseases and its diagnostic and prognostic value, and we explain the mechanism by which NNT-AS1 regulates cancer progression by competing with miRNAs. In addition, we also reveal the correlation between NNT-AS1 and cisplatin resistance and the potential clinical applications of NNT-AS1.


Gene ◽  
2019 ◽  
Vol 701 ◽  
pp. 121-124 ◽  
Author(s):  
Mohammad Reza Safari ◽  
Fatemeh Mohammad Rezaei ◽  
Arash Dehghan ◽  
Rezvan Noroozi ◽  
Mohammad Taheri ◽  
...  

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Anqiang Yang ◽  
Handong Wang ◽  
Xiaobing Yang

Human glioma is one of the malignant tumors of the central nervous system (CNS). Its prognosis is poor, which is due to its genetic heterogeneity and our poor understanding of its underlying molecular mechanisms. The present study aimed to assess the relationship between plasmacytoma variant translocation 1 (PVT1) and enhancer of zeste homolog 2 (EZH2), and their effects on the proliferation and invasion of glioma cells. The expression levels of PVT1 and EZH2 in human glioma tissues and cell lines were measured using quantitative RT-PCR (qRT-PCR). Then, after siRNA-PVT1 and entire PVT1 sequence vector transfection, we determined the regulation roles of PVT1 in the proliferation, apoptosis, migration, and invasion of glioma cells. We found that the expression levels of both PVT1 and EZH2 were up-regulated in human glioma tissues and cell lines, and positively correlated with glioma malignancy. And, silencing of PVT1 expression resulted in decreased proliferation, increased apoptosis, and decreased migration and invasion. In addition, exogenous PVT1 led to increased EZH2 expression and increased proliferation and induced proliferation and invasion. These data inferred that long non-coding RNA PVT1 could be served as an indicator of glioma prognosis, and PVT1–EZH2 regulatory pathway may be a novel therapeutic target for treating glioma.


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