Molecular screening for nigericin treatment in pancreatic cancer by high-throughput RNA sequencing

2020 ◽  
Author(s):  
Zhihua Xu ◽  
Qiaoming Zhi ◽  
Guanzhuang Gao ◽  
Fei Liu ◽  
Ye Han ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Throughput ◽  
Underlying Mechanism ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Bioinformatics Analyses ◽  
Non Coding Rna ◽  
Anti Cancer ◽  
Trans Regulation ◽  
Cis And Trans

Abstract Background Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that nigericin could inhibited the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA.Methods The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing.Results Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including GO and KEGG analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and PPI network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the nigericin anti-cancer process.Conclusion These findings provided new insight into the molecular mechanism of nigericin toward cancer cells, and suggested a possible clinical application in PC.

scholarly journals High-throughput sequencing of circRNAs reveals novel insights into mechanisms of nigericin in pancreatic cancer

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhihua Xu ◽  
Jiaqing Shen ◽  
Shangbo Hua ◽  
Daiwei Wan ◽  
Qian Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Expression Profiles ◽  
Potential Functions ◽  
Differentially Expressed ◽  
Pcr Analysis ◽  
Signal Pathways ◽  
Sequencing Data ◽  
Anti Cancer

Abstract Background Our previous study had proved that nigericin could reduce colorectal cancer cell proliferation in dose- and time-dependent manners by targeting Wnt/β-catenin signaling. To better elucidate its potential anti-cancer mechanism, two pancreatic cancer (PC) cell lines were exposed to increasing concentrations of nigericin for different time periods, and the high-throughput sequencing was performed to explore the circRNA expression profiles after nigericin exposure on pancreatic cancer (PC) cells. Results In this study, a total of 183 common differentially expressed circRNAs were identified, and the reliability and validity of the sequencing data were verified by the PCR analysis. According to the parental genes of circRNAs, the GO analysis was performed to predict the most enriched terms in the biological process, cellular components and molecular functions. The KEGG analysis and pathway-pathway network exhibited the potential signal pathways and their regulatory relationships. Meanwhile, a potential competing endogenous RNA (ceRNA) mechanism through a circRNA-miRNA-mRNA network was applied to annotate potential functions of these common differentially expressed circRNAs, and these predicted miRNAs or mRNAs might be involved in nigericin damage. Conclusions By the bioinformatics method, our data will facilitate the understanding of nigericin in PC cells, and provide new insight into the molecular mechanism of nigericin toward cancer cells. This is the first report that discusses the potential functions of nigericin in cancers through the bioinformatics method. Our data will facilitate the understanding of nigericin-mediated anti-cancer mechanisms in PC.

scholarly journals Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

2021 ◽  
Vol 22 (14) ◽  
pp. 7477
Author(s):  
Rok Razpotnik ◽  
Petra Nassib ◽  
Tanja Kunej ◽  
Damjana Rozman ◽  
Tadeja Režen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Protein ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Bioinformatics Analyses ◽  
Published Evidence

Circular RNAs (circRNAs) are increasingly recognized as having a role in cancer development. Their expression is modified in numerous cancers, including hepatocellular carcinoma (HCC); however, little is known about the mechanisms of their regulation. The aim of this study was to identify regulators of circRNAome expression in HCC. Using publicly available datasets, we identified RNA binding proteins (RBPs) with enriched motifs around the splice sites of differentially expressed circRNAs in HCC. We confirmed the binding of some of the candidate RBPs using ChIP-seq and eCLIP datasets in the ENCODE database. Several of the identified RBPs were found to be differentially expressed in HCC and/or correlated with the overall survival of HCC patients. According to our bioinformatics analyses and published evidence, we propose that NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are candidate regulators of circRNA expression in HCC. We confirmed that the knocking down the epithelial splicing regulatory protein 2 (ESRP2), known to be involved in the maintenance of the adult liver phenotype, significantly changed the expression of candidate circRNAs in a model HCC cell line. By understanding the systemic changes in transcriptome splicing, we can identify new proteins involved in the molecular pathways leading to HCC development and progression.

scholarly journals Identification of Non-coding RNA Biomarkers in Stress-induced Depression via Comprehensive Analysis of Competing Endogenous RNA Network

2020 ◽  
Author(s):  
xuanjun liu ◽  
Lan Yan ◽  
Chun Lin ◽  
Yiliang Zhang ◽  
Haofei Miao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Psychiatric Disease ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Promising Perspective

Abstract BackgroundDepression is one of the most common psychiatric disease worldwide. Although the research about the pathogenesis of depression have achieved progress, the detailed effect of non-coding RNAs (ncRNAs) in depression are still not clearly elucidated. This study was aimed to identify non-coding RNA biomarkers in stress-induced depression via comprehensive analysis of competing endogenous RNA networkMethodsIn this present study, we acquired RNA expression from RNA seq expression profile in three mice with depressive-like behaviors using chronic restraint stress paradigm and three C57BL/6J wild-type mice as control mice. ResultsA total of 41 differentially expressed circular RNAs (circRNAs) and 181 differentially expressed messenger RNAs (mRNAs) were up-regulated, and 65 differentially expressed circRNAs and 289 differentially expressed mRNAs were down-regulated, which were selected by a threshold of fold change ≥2 and a p-value < 0.05. Gene Ontology was performed to analyze the biological functions, and we predicted potential signaling pathways based on Kyoto Encyclopedia of Genes and Genomes pathway database. In addition, we constructed a circRNA-microRNA (miRNA)-mRNA regulatory network to further identify non-coding RNAs biomarkers. ConclusionsOur findings provide a promising perspective for further research into molecular mechanisms of depression, and targeting circRNA -mediated competing endogenous RNA (ceRNA) network is a useful strategy to early recognize the depression.

scholarly journals seekCRIT: Detecting and characterizing differentially expressed circular RNAs using high-throughput sequencing data

2020 ◽  
Vol 16 (10) ◽  
pp. e1008338
Author(s):  
Mohamed Chaabane ◽  
Kalina Andreeva ◽  
Jae Yeon Hwang ◽  
Tae Lim Kook ◽  
Juw Won Park ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Sequencing Data ◽  
High Throughput Sequencing Data

Identification of differentially expressed circular RNAs in human nasopharyngeal carcinoma

2020 ◽  
Vol 29 (4) ◽  
pp. 483-492
Author(s):  
Hanwei Wu ◽  
Yuchen Liu ◽  
Hongfang Duan ◽  
Xiaoqin Fan ◽  
Yujie Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Ras Signaling ◽  
Epstein Barr Virus Infection ◽  
Bioinformatics Analyses ◽  
Gene Map ◽  
Barr Virus ◽  
Epstein Barr

BACKGROUND: Circular RNAs (circRNAs) are endogenous RNAs that have a covalent closed cycle configuration. circRNAs have been found to be differentially expressed in many human cancers. Therefore, circRNAs may be ideal biomarkers for the diagnosis and treatment of cancer. However, we know very little about the function of circRNAs in nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the circRNA expression profiles in NPC. METHODS: We utilized high-throughput RNA sequencing (RNA-Seq) to evaluate the circRNA expression profile in NPC A total of 13,561 unique circRNA candidates were detected. Selection of aberrantly expressed circRNAs was carried out using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. We carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to identify the biological functions of differentially expressed circRNAs. Moreover, bioinformatics analyses were implemented to predict the effects between circRNAs and cancer-related microRNAs (miRNAs), and we used Cytoscape to build a cancer-related circRNA-miRNA target gene map. Finally, to verify dysregulated circRNAs, quantitative real-time PCR was utilized. RESULTS: In NPC tissues, we found that 73 circRNAs were downregulated and 59 were upregulated. The top 12 candidate circRNAs were selected from several vital NPC pathways such as the human papillomavirus and Epstein-Barr virus infection signaling pathways (hsa05165 and hsa05169, respectively), Hepatitis B (hsa05161), and the Ras signaling pathway (hsa04014). A network map of circRNA-miRNA interactions of 12 differentially expressed circRNAs was built. Hsa_circ_0007637 expression distinguished NPC tissues from paired healthy tissues and NPC cell lines (HNE1 6-10B, 5-8F, CNE-2, and so on) from a normal epithelial (NP460) cell line. CONCLUSIONS: In this study, we investigated the profiles of differentially expressed circRNAs in NPC, and our results show that hsa_circ_0007637 may be a biomarker for NPC and play a role in its development. This observation-based research identified dysregulated circRNAs in NPC, which may assist in the development of biomarkers for this disease. Further studies on the mechanisms and functions of these circRNAs may promote our understanding of NPC tumorigenesis.

scholarly journals Integrated Analysis of a circRNA-miRNA-mRNA Axis in Intervertebral Disc Degeneration

2020 ◽  
Author(s):  
Laifu Wei ◽  
Bizhi Tu ◽  
Fei Gao ◽  
Jun Qian
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Underlying Mechanism ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Integrated Analysis ◽  
Control Group ◽  
Common Symptom ◽  
Sequencing Data

Abstract Background: Low back pain (LBP) is a common symptom in daily life and one of the primary causes is intervertebral disc degeneration (IDD). Growing studies have indicated that circular RNAs (circRNAs) are intimately associated with IDD; however, the underlying mechanism has not yet been elucidated. We aimed to explore how circRNAs regulate IDD in an effort to provide novel insight for clinical diagnosis and treatment. Methods: The sequencing data of circRNAs, microRNAs (miRNAs), and mRNA were acquired from Gene Expression Omnibus (GEO) datasets. By analyzing the dataset consisting of a control group and degenerated group, differentially expressed circRNAs, miRNAs, and mRNAs were collected, and then the intersection of circRNAs, miRNAs, and mRNAs was screened. According to these intersectional RNAs, we constructed an integrally circRNA-miRNA-mRNA network. Finally, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we further clarified functions of the intersectional mRNA in IDD. Results: we obtained 620 differentially expressed circRNAs(DEcircRNAs), 13 miRNA (DEmiRNA), 273 mRNAs(DEmRNAs), 12 intersectional miRNAs, and 47 intersectional mRNAs. Finally, based on interactional 8 circRNA, 5 miRNAs and 15 mRNAs, an integrally circRNA-miRNA-mRNA network was constructed. Eight circRNAs, contained hsa_circ_0032254, hsa_circ_0003183, hsa_circ_0032253, hsa_circ_0001293, hsa_circ_0004565, hsa_circ_0091570, hsa_circ_0077526, and hsa_circ_0057552, may regulate IDD onset and progression by acting as competing endogenous RNAs. The results of GO and KEGG analyses implied that the targeted genes might significantly correlate to IDD.Conclusion: our findings improved a better understanding of the circRNA-related ceRNA regulatory mechanism in IDD and offered possible targets for IDD treatment.

scholarly journals Circular RNA EPB41 Expression Predicts Unfavorable Prognoses in NSCLC by Regulating miR-486-3p/eIF5A Axis-Mediated Stemness

2021 ◽  
Author(s):  
Xiyu Liu ◽  
Yue Wu ◽  
Yuqing Lou ◽  
Mingming Jin ◽  
Xue Li ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Expression Profiles ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Reporter System ◽  
Bioinformatics Analyses

Abstract Dysregulation of circular RNAs (circRNAs) has recently been found to play an important role in the progression and development of cancers such as non-small cell lung cancer (NSCLC). Yet the functions of many circRNAs in NSCLC remain unclear. In this study, the circRNA expression profiles in NSCLC tumor tissues and adjacent non-tumorous tissues were detected by high-throughput sequencing. Bioinformatics analyses, the dual-luciferase reporter system, fluorescence in situ hybridization (FISH) and miRNA/mRNA high-throughput sequencing were used to identify circ-EPB41 and its downstream target. The subcutaneous tumor/caudal vein transfer mouse model was used for tumor growth and invasion analysis. The results show that the circ-EPB41 was upregulated in NSCLC tissues and cell lines. Increased circ-EPB41 expression in NSCLC was significantly correlated with malignant characteristics, and positive to post-surgical overall survival of NSCLC patients. Reduced circ-EPB41 expression in NSCLC decreased cell proliferation and invasion in both in vitro and in vivo experiments. The miRNA/mRNA high-throughput sequencing suggested that downregulation of circ-EPB41 promoted microRNA (miR)-486-3p and suppressed eukaryotic translation initiation factor 5A (eIF5A) expression. Luciferase reporter experiments confirmed that miR-486-3p/eIF5A were downstream targets of circ-EPB41. In addition, we also found that downregulation of circ-EPB41 suppressed self-renewal and decreased expression of stemness markers SOX2, OCT-4, Nanog and CD133 by sponging miR-486-3p to enhance eIF5A expression. Taken togeter, these data revealed the important role of circ-EPB41 in regulating NSCLC cell invasion and proliferation by modifying miR-486-3p/eIF5A axis-mediated stemness. We believe our study provides a novel perspective regarding the role of circRNAs in NSCLC progression.

scholarly journals Regulatory role of non-coding RNA in ginseng rusty root symptom tissue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xingbo Bian ◽  
Pengcheng Yu ◽  
Ling Dong ◽  
Yan Zhao ◽  
He Yang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Regulatory Networks ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Primary Metabolism ◽  
Non Coding Rna

AbstractGinseng rusty root symptom (GRS) is one of the primary diseases of ginseng. It leads to a severe decline in the quality of ginseng and significantly affects the ginseng industry. The regulatory mechanism of non-coding RNA (ncRNA) remains unclear in the course of disease. This study explored the long ncRNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) in GRS tissues and healthy ginseng (HG) tissues and performed functional enrichment analysis of the screened differentially expressed ncRNAs. Considering the predictive and regulatory effects of ncRNAs on mRNAs, we integrated ncRNA and mRNA data to analyze and construct relevant regulatory networks. A total of 17,645 lncRNAs, 245 circRNAs, and 299 miRNAs were obtained from HG and GRS samples, and the obtained ncRNAs were characterized, including the classification of lncRNAs, length and distribution of circRNA, and the length and family affiliations of miRNAs. In the analysis of differentially expressed ncRNA target genes, we found that lncRNAs may be involved in the homeostatic process of ginseng tissues and that lncRNAs, circRNAs, and miRNAs are involved in fatty acid-related regulation, suggesting that alterations in fatty acid-related pathways may play a key role in GRS. Besides, differentially expressed ncRNAs play an essential role in regulating transcriptional translation processes, primary metabolism such as starch and sucrose, and secondary metabolism such as alkaloids in ginseng tissues. Finally, we integrated the correlations between ncRNAs and mRNAs, constructed corresponding interaction networks, and identified ncRNAs that may play critical roles in GRS. These results provide a basis for revealing GRS's molecular mechanism and enrich our understanding of ncRNAs in ginseng.

scholarly journals Bioinformatics Analysis of Circular RNA Expression Profiles in HBx-Transfected HepG2 Cells by Transcriptional Sequencing

2021 ◽  
Author(s):  
Luzheng Liu ◽  
Jiacheng Chen ◽  
Liang Chen ◽  
Cheng Chen ◽  
Dafeng Xu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Hepg2 Cells ◽  
Target Genes ◽  
Expression Profiles ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Bioinformatics Analyses ◽  
Go Analysis ◽  
Micro Rnas

Abstract BACKGROUND Circular RNA (CircRNA) and HBx genes separately play essential roles in the occurrence and development of hepatitis B (HBV)-related hepatocellular carcinoma (HCC). However, whether HBx expression in HCC is co-related to differential circRNA patterns remains unknown. METHODS HCC cell lines with HBx overexpression (HepG2 H6679) and empty vector control (HepG2 H5298) were successfully constructed. The high-throughput second-generation transcriptome sequencing technology (RNA-seq) was employed to sequence the two cell lines, and the selected circRNAs were verified by qPCR (quantitative real-time PCR). The differentially expressed circRNAs were analyzed. Bioinformatics analyses, including clustering, differential expression, GO analysis, and KEGG pathway, were performed. Target Scan and Miranda software were employed to predict miRNAs corresponding with circRNAs. RESULTS We identified 1120 circRNAs upregulated and 1447 circRNAs downregulated in HepG2 cell lines with HBx overexpression compared to its control. We selected 36 circRNAs with significant differences (also consistent with log2fold change absolute value ≥ 1.0 or P ≤ 0.05) displayed by cluster analysis and then performed qPCR validation. Among them, 15 circRNAs (hsa_circ_0005603, hsa_circ_0004448, hsa_circ_0006845, hsa_circ_0064654, hsa_circ_0006460, hsa_circ_0045350, hsa_circ_0000824, hsa_circ_0005227, hsa_circ_0067991, hsa_circ_0064656, hsa_circ_0005224, circRNA11716, circRNA759, circRNA14848 and circRNA13751) are consistent with sequencing results. Hsa_circ_0005603 and hsa_circ_0006845 showed significant differences and were chosen for further study. GO analysis shows that many target genes are involved in biological processes, cellular components, and molecular functions. Nearly 193 target genes were enriched on KEGG pathways analysis. Actin cytoskeleton regulation, tight junction, and FoxO signaling pathway are among the top three pathways involved in most genes. We predicted that hsa_circ_0005603 might interact with micro-RNAs, including miR-182-5p, hsa-miR-27a-3p, hsa-miR-98-5p, and hsa-miR-198, that might thereby regulate downstream genes involved in tumor progression. Similarly, hsa_circ_0006845 was predicted to be referred to HBV-related HCC by acting as a sponge for hsa-miR-106a-3p and hsa-miR-198. Furthermore, we discovered two novel circular RNAs (circRNA11716 and circRNA13751) which might be involved in HCC occurrence. CONCLUSION In this study, we comprehensively explored the differentially expressed circRNAs in HepG2 cells with different HBx expression, and our results indicate that hsa_circ_0005603, hsa_circ_0006845, and novel circular RNAs (circRNA11716 and circRNA13751) might play an important role in HBV-related HCC, deserving further research.

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