scholarly journals Clinical Significance of Long Non-Coding RNA HCG18, OIP5-AS1, FGD5-AS1 and LINC00657 Expression in Human Gastric Cancer

Author(s):  
Ali Zareh ◽  
Elmira Rabani ◽  
Hamed Zare ◽  
Mohammad Heiat ◽  
Hamid Bakherad

Abstract Background Gastric cancer (GC) is a major health problem and the third cause of cancer-induced deaths globally. Long non-coding RNAs (lncRNAs) are new cellular regulators in cancers whose contribution to GC carcinogenesis is still unknown to a large extent. This study aimed to investigate expression levels of bioinformatically ranked lncRNAs in GC tissues. Methods Using a bioinformatic approach, lncRNAs supposed to be involved in GC tumorigenesis were prioritized. Further, the top-ranked lncRNAs including HCG18, OIP5-AS1, FGD5-AS1, and LINC00657 were selected for experimental validation. Moreover, qPCR was used to validate bioinformatics findings in 35 GC and 35 paired adjacent normal gastric tissue samples (ANGTs). Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were generated to assess the diagnostic values of the lncRNAs. Results lncRNA-HCG18 showed to be the top-ranked lncRNA involved in GC, as identified by bioinformatics analysis. Additionally, HCG18, OIP5-AS1, FGD5-AS1, and LINC00657 expression levels significantly increased in GC tissue samples compared to ANGTs. The area under the curve (AUC) of HCG18, OIP5-AS1, FGD5-AS1, and LINC00657 were 0.80, 0.74, 0.73, and 0.71, respectively. Considering the findings, it was concluded that HCG18, OIP5-AS1, FGD5-AS1, and LINC00657 lncRNAs may contribute to GC tumorigenesis. Conclusion This study also found that the bioinformatic approach could be applied as an efficient approach to finding candidate lncRNAs relevant to GC progression.

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 302 ◽  
Author(s):  
Xin Zhang ◽  
Yao Qin ◽  
Zhaohai Pan ◽  
Minjing Li ◽  
Xiaona Liu ◽  
...  

The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties. The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells. We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells. Further investigation showed that CBD significantly upregulated ataxia telangiectasia-mutated gene (ATM) and p53 protein expression and downregulated p21 protein expression in SGC-7901 cells, which subsequently inhibited the levels of CDK2 and cyclin E, thereby resulting in cell cycle arrest at the G0–G1 phase. In addition, CBD significantly increased Bax expression levels, decreased Bcl-2 expression levels and mitochondrial membrane potential, and then upregulated the levels of cleaved caspase-3 and cleaved caspase-9, thereby inducing apoptosis in SGC-7901 cells. Finally, we found that intracellular reactive oxygen species (ROS) increased after CBD treatment. These results indicated that CBD could induce G0–G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.


Author(s):  
Dongmei Zhan ◽  
Tengyang Ni ◽  
Haibo Wang ◽  
Mengying Lv ◽  
Masataka Sunagawa ◽  
...  

Background: This study aimed to determine the effect and mechanism of Celastrol inhibiting the proliferation and decreases drug resistance of cisplatin-resistant gastric cancer cells. Objective: To explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP. Methods: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatin-resistant cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug resistance index (DRI). According to the half inhibitory concentration (IC50) value, the action concentration of the following experimental drugs was set to reduce the cytotoxicity; Annexin V-FITC/PI double staining method was used to detect the apoptosis of SGC7901/DDP cells induced by Celastrol; Western Blot was used to examine the expression levels of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin (mTOR) pathway related proteins; Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP. Results: (1) Compared with the control group (We set the untreated group as the control group), the proliferation of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4μmol/L Celastrol in a time- and concentration-dependent manner (P<0.05). The Drug resistance index DRI of the SGC7901/DPP cells to DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However, after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced the expression of the mTOR signaling pathway related proteins, suggesting that the mTOR signaling pathway may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp, MRP1, and BCRP in the SGC7901/DPP cells. Conclusion: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the mTOR signaling pathway.


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.


2020 ◽  
Author(s):  
Fang Cao ◽  
Yongwei Hu ◽  
Zaichang Chen ◽  
Wei Han ◽  
Weijie Lu ◽  
...  

Abstract Background: Recent researches have suggested that long non-coding RNA (lncRNA) is involved in the tumorigenesis and development of stomach cancer (SC). This meta-analysis aimed to identify the diagnostic performance of circulating lncRNAs in SC.Methods: All relevant studies were systematically searched through PubMed, Web of Science, Cochrane Library and EMBASE databases. The diagnostic values of lncRNAs were mainly assessed by pooled sensitivity (SEN), specificity (SPE), and summary receiver operating characteristic area under the curve (SROC AUC). Meta-DiSc 1.4, Review Manager 5.3 and STATA 12.0 were used for statistical analysis. Results: A total of 42 eligible studies were included in this meta-analysis. The pooled SEN, SPE, and AUC were 0.78 (95%CI: 0.75-0.81), 0.75 (95%CI: 0.71-0.78), and 0.83 (95%CI: 0.80-0.86) respectively, suggesting that the lncRNAs test had a high accuracy for the diagnosis of SC. Obvious heterogeneity might come from the type of lncRNA through subgroup and meta-regression analysis. Fagan diagram showed the clinical value of lncRNAs test in SC. Conclusions: Abnormal expression of circulating lncRNAs exhibits a high efficacy for diagnosing SC, which is promising in clinical application.


2021 ◽  

Background: Gastric cancer (GC) is the most prevalent malignancy worldwide and a common cause of death in Iran. Studies have proved that a variety of dysregulated microRNAs is involved in the development and progression of gastric cancer. The present study aimed to evaluate the expression levels of plasma circulating oncogenic miR-21 and miR-192 and their association with clinical phenotypes of patients with gastric cancer in the north of Iran. Material and Methods: Clinico-pathological analysis was conducted using a standard protocol and pathological tests. The expression levels of miR-21 and miR-192 were measured using quantitative reverse transcription-polymerase chain reaction in the plasma of twenty pre/post-operative gastric cancer patients and twenty healthy subjects. The receiver operating characteristic (ROC) curve of these microRNAs was analyzed to investigate their diagnosis properties. Results: The study results indicated that plasma miR-21 expression was significantly associated with tumor stage and helicobacter pylori infection status (P=0.024, P=0.0004, respectively). However, no association was observed between clinic-pathological characteristics and miR-192 expression. The results showed that the plasma levels of miR-21 (P=0.0001) and miR-192 (P=0.0007) were significantly higher in GC patients compared to those in healthy individuals. Furthermore, the ROC analyses yielded the area under the curve (AUC) values of 0.9525±0.03 (P<0.0001) and 0.5925±0.09 (P=0.316) for miR-21and miR-192, respectively. Pearson regression analysis showed that there was no significant correlation between the expression of miR-21 and miR-192 (P=0.1507). Conclusion: Based on the obtained results, the expression of the plasma level of miR-21 was significantly higher in gastric cancer patients compared to that in the healthy group. Furthermore, the higher levels of AUC in miR-21 indicated the potential role of miR-21 as a noninvasive biomarker for the prognosis of gastric cancer in the population of the north of Iran.


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.


2020 ◽  
Vol 34 (3) ◽  
Author(s):  
Xiuchong Yu ◽  
Haixiang Ding ◽  
Liangwei Yang ◽  
Yu Yu ◽  
Jiaming Zhou ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Zirui Meng ◽  
Minjin Wang ◽  
Shuo Guo ◽  
Yanbing Zhou ◽  
Mengyuan Lyu ◽  
...  

IntroductionThe insufficient understanding and misdiagnosis of clinically diagnosed pulmonary tuberculosis (PTB) without an aetiological evidence is a major problem in the diagnosis of tuberculosis (TB). This study aims to confirm the value of Long non-coding RNA (lncRNA) n344917 in the diagnosis of PTB and construct a rapid, accurate, and universal prediction model.MethodsA total of 536 patients were prospectively and consecutively recruited, including clinically diagnosed PTB, PTB with an aetiological evidence and non-TB disease controls, who were admitted to West China hospital from Dec 2014 to Dec 2017. The expression levels of lncRNA n344917 of all patients were analyzed using reverse transcriptase quantitative real-time PCR. Then, the laboratory findings, electronic health record (EHR) information and expression levels of n344917 were used to construct a prediction model through the Least Absolute Shrinkage and Selection Operator algorithm and multivariate logistic regression.ResultsThe factors of n344917, age, CT calcification, cough, TBIGRA, low-grade fever and weight loss were included in the prediction model. It had good discrimination (area under the curve = 0.88, cutoff = 0.657, sensitivity = 88.98%, specificity = 86.43%, positive predictive value = 85.61%, and negative predictive value = 89.63%), consistency and clinical availability. It also showed a good replicability in the validation cohort. Finally, it was encapsulated as an open-source and free web-based application for clinical use and is available online at https://ziruinptb.shinyapps.io/shiny/.ConclusionCombining the novel potential molecular biomarker n344917, laboratory and EHR variables, this web-based prediction model could serve as a user-friendly, accurate platform to improve the clinical diagnosis of PTB.


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