Bioinformatics Analysis of Differently Expressed Mirnas in CD5 Positive Relapsed and Refractory Diffuse Large B-Cell Lymphoma and Their Potential Theoretical and Clinical Investigations

Introduction: CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by a poor prognosis, poorly respond to the regulatory treatment strategy, and a relatively high incidence of central nervous system (CNS) infiltration. In this study, we aim to identify key differentially expressed miRNAs (DE-miRNAs) and their target genes in the peripheral blood of CD5+ refractory and relapsed (CD5+ R/R DLBCL) patients. The relationship of the DE-miRNAs and the pathogenesis of CD5+ R/R DLBCL will also be analyzed by bioinformatics tools. Methods: Three female patients with confirmed CD5+ R/R DLBCL were enrolled in this study, their age were 38, 62 and 65 years old, respectively. Three healthy female adults aged 42, 55 and 61, respectively were selected as the control group. The peripheral venous blood of them was collected for RNA extraction and standard small RNA sequencing. Differentially expressed miRNAs analysis was performed with R package edgeR. The target genes of DE-miRNAs were predicted by miRNet. A protein protein interaction (PPI) network was established for these target genes through string database. Functional annotation and pathway enrichment analyses for the target genes were performed through DAVID database to identify their potential functions, target genes, and pathways they might be involved in. Results: 1. Scatter plots, Volcano plots and Heat-maps were used to visualize miRNAs of Differentially expressed genes. As shown in Fig.1, Fig. 2 and Fig. 3. 2. Fifty-five sequences were significantly upregulated and 23 were significantly downregulated in patients with CD5+ R/R DLBCL.Among the candidate miRNAs, 11 up-regulated genes and 4 down-regulated genes were selected according to the log2FC value. The target genes of 11 potential up-regulated and 4 down-regulated DE-miRNAs were successively predicted by As shown in Table 1, a total of 439 and 632 predicted targets of the up-regulated and down-regulated DE-miRNAs were identified, respectively. 3. PPI networks of predicted target genes of 11 upregulated DE-miRNAs (Fig.4a) and 4 downregulated DE-miRNAs (Fig. 4b) were separately constructed using the STRING database and Cytoscape software. According to a degree, the top 10 hub genes in the networks were screened out and were listed inTable 2. Six important hub genes were identified, including two target genes predicted by up-regulating DE-miRNAs, namely NRAS and PIK3R1, and four target genes predicted by down-regulating DE-miRNAs, namely EGFR, VEGFA, IGF1 and Grb2. 4. DAVID now provides a comprehensive set of functional annotation tools for investigators to understand biological meaning. GO analysis was divided into three functional groups, including molecular function (MF), biological processes (BP), and cell composition (CC). The top 10 GO terms of targets of up-regulated DE-miRNAs were presented in Fig.5a-c. The top 10 GO terms of targets of down-regulated DE-miRNAs were shown in Fig. 5d-f. 5. Based on the KEGG database, we analyzed the pathways in which the differentially expressed target genes were involved in. As shown in Fig. 6a-b. The targets of up-regulated DE-miRNAs were enriched in pathways in cancer, oxytocin signaling pathway, ErbB signaling pathway, Rap1 signaling pathway, and proteoglycans in cancer. Whereas the targets of down-regulated DE-miRNAs were enriched in pathways in cancer, Ras signaling pathway, and PI3K-Akt signaling pathway. Conclusions: In this study, we analyzed the differentially expressed miRNAs in CD5+ R/R DLBCL patients, identified their potential functions, target genes, and pathways they might be involved in. This study found that ErbB signaling pathway, Rap1 signaling pathway, Ras signaling pathway and PI3K Akt signaling pathway were the most frequently involved pathways of miRNAs related genes. Target genes including NRAS, PIK3R1, EGFR, VEGFA, IGF1, and Grb2 might have a close relationship in the pathogenesis of CD5+ R/R DLBCL. New targeted drugs related to these pathways and genes may be beneficial to the treatment of CD5+ DLBCL. Our preliminary informatic results might be helpful to deeply understand the pathogenesis and chemotherapy resistance mechanism of CD5+ R/R DLBCL. In the future, we will verify our preliminary informatic results in pathological tissues from patients with CD5+ DLBCL in larger samples. Disclosures No relevant conflicts of interest to declare.

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MicroRNA expression profiling involved in Borax-induced anti-tumor effect using gene-chip analysis

10.21203/rs.2.20621/v1 ◽

2020 ◽

Author(s):

Lun Wu ◽

Ying Wei ◽

Wen-Bo Zhou ◽

Jiao Zhou ◽

Li-Hua Yang ◽

...

Keyword(s):

Signaling Pathway ◽

Hepg2 Cells ◽

Enrichment Analysis ◽

Gene Chip ◽

Differentially Expressed ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Ras Signaling ◽

Therapeutic Benefits ◽

Differentially Expressed Mirnas

Abstract Background Borax, a boron compound, which is becoming widely recognized for its biological effects, including antioxidant activity, cytotoxicity, and potential therapeutic benefits. However, the specific molecular mechanisms underlying borax-induced anti-tumor effect still remain to be to further elucidated. MicroRNAs (miRNAs) may play key roles in cellular processes including tumor progression, cell apoptosis and cytotoxicity. Thus, this study aimed to investigate, whether miRNAs were involved in the borax-mediated anti-tumor effect using miRNA profiling of a human liver cancer cell line (HepG2) using gene-chip analysis.Methods Total RNA was extracted and purified from HepG2 cells that were treated with 4 mM borax for either 2 or 24 h. The samples underwent microarray analysis using an Agilent Human miRNA Array. Differentially expressed miRNAs were analysed by volcano plot and heatmap, and were validated using real-time fluorescent quantitative PCR (qPCR).ResultsAmong this, 2- or 24-h exposure to borax significantly altered the expression level of miRNAs in HepG2 cells, 4 or 14 were upregulated and 3 were downregulated compared with the control group, respectively (≥2-fold; P<0.05). GO enrichment analysis and KEGG pathway enrichment analysis revealed that target genes of differentially expressed miRNAs in HepG2 cells predominantly participated in MAPK signaling pathway, TGF-beta signaling pathway, NF-kappa B signaling pathway, etc; in 2-h borax treatment group, while Ras signaling pathway, FoxO signaling pathway, Cellular senescence, etc; involved in 24-h treatment group.Conclusions Result indicates that borax-induced anti-tumor effect may be associated with alterations in miRNAs.

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Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

PeerJ ◽

10.7717/peerj.10470 ◽

2021 ◽

Vol 9 ◽

pp. e10470

Author(s):

Wanzhen Li ◽

Shiqing Liu ◽

Shihong Su ◽

Yang Chen ◽

Gengyun Sun

Keyword(s):

Lung Adenocarcinoma ◽

Signaling Pathway ◽

Prognostic Value ◽

Target Genes ◽

Predictive Accuracy ◽

Differentially Expressed ◽

Prognostic Signature ◽

Tissue Samples ◽

Gene Set ◽

Differentially Expressed Mirnas

MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.

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Analysis of MicroRNA Transcriptomes Insights into the miR-148a-3p Inducer of Rumen Development in Goats

10.21203/rs.3.rs-40834/v1 ◽

2020 ◽

Author(s):

Tao Zhong ◽

Cheng Wang ◽

Jiangtao Hu ◽

Xiaoyong Chen ◽

Lili Niu ◽

...

Keyword(s):

Signaling Pathway ◽

Target Genes ◽

Genetic Regulation ◽

Mapk Signaling ◽

Regulation Mechanism ◽

Ras Signaling ◽

Genome Wide ◽

A Genome ◽

Differentially Expressed Mirnas ◽

And Function

Abstract Background: Rumen is an important digestive organ of ruminant. From fetal to adult stage, the morphology, structure and function of rumen have changed significantly. But the intrinsic genetic regulation is still limited. We previously reported a genome-wide expression profile of miRNAs in prenatal goat rumens. In the present study, we rejoined analyzed the transcriptomes of rumen miRNAs during prenatal (E60 and E135) and postnatal (D30 and D150) stages.Results: A total of 66 differentially expressed miRNAs (DEMs) were identified in the rumen tissues from D30 and D150 goats. Of these, 17 DEMs were consistently highly expressed in the rumens at the preweaning stages (E60, E135 and D30), while down-regulated at D150. Noteworthy, annotation analysis revealed that the target genes regulated by the DEMs were mainly enriched in MAPK signaling pathway, Jak-STAT signaling pathway and Ras signaling pathway. Interestingly, the expression of miR-148a-3p was significantly high in the embryonic stage and down-regulated at D150. The potential binding sites between miR-148a-3p and QKI were predicted by the TargetScan and verified by the dual luciferase report assay. The co-localization of miR-148a-3p and QKI was observed not in intestinal tracts but in rumen tissues by in situ hybridization. Moreover, the expression of miR-148a-3p in the epithelium was significantly higher than that in the other layers, suggesting that miR-148a-3p involve in the development of rumen epithelial cells by targeting QKI. Subsequently, miR-148a-3p inhibitor was found to induce the proliferation of GES-1 cells.Conclusions: Taken together, these results identified the DEMs involved in the development of rumen and provided an insight into the regulation mechanism of goat rumens during development.

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miR-429 Suppresses Proliferation and Migration in Glioblastoma Cells and Induces Cell-cycle Arrest via Modulating Several Target Genes of ERBB Signaling Pathway

10.21203/rs.3.rs-186982/v1 ◽

2021 ◽

Author(s):

Fatemeh Gheidari ◽

Ehsan Arefian ◽

Mahboubeh Kabiri ◽

Ehsan Seyedjafari ◽

Ladan Teimoori-Toolabi ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

Target Genes ◽

Cycle Arrest ◽

Cell Proliferation And Migration ◽

Erbb Signaling ◽

And Migration ◽

Erbb Signaling Pathway ◽

Proliferation And Migration

Abstract Glioblastoma is aggressive and lethal brain cancer, which is incurable by cancer standard treatments. miRNAs have great potential to be used for gene therapy due to their ability to modulate several target genes simultaneously. We found miR-429 is downregulated in glioblastoma and has several predicted target genes from the ERBB signaling pathway using bioinformatics tools. ERBB is the most over-activated genetic pathway in glioblastoma patients, which is responsible for augmented cell proliferation and migration in glioblastoma multiforme (GBM). Here we overexpressed miR-429 using lentiviral vectors in GBM U-251 cells and observed that the expression level of several oncogenes of the ERBB pathway, EGFR, PIK3CA, PIK3CB, KRAS, and MYC significantly decreased; as shown by real-time PCR and western blotting. Using the luciferase assay, we showed that miR-429 directly targets MYC, BCL2, and EGFR. In comparison to scrambled control, miR-429 had a significant inhibitory effect on cell proliferation and migration as deduced from MTT and scratch wound assays and induced cell-cycle arrest in flow cytometry. Altogether miR-429 seems to be an efficient suppressor of the ERBB genetic signaling pathway and a potential therapeutic for glioblastoma.

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miR-145 plays a role in mitochondria dysfunction in alveolar epithelial cells in LPS-induced ARDS

10.21203/rs.2.11952/v1 ◽

2019 ◽

Author(s):

Yi Han ◽

Sucheng Mu ◽

Jianli Wang ◽

Wei Wei ◽

Ming Zhu ◽

...

Keyword(s):

Epithelial Cells ◽

Signaling Pathway ◽

Target Genes ◽

Intratracheal Instillation ◽

Alveolar Epithelial Cells ◽

Ras Signaling ◽

Regulation Of Transcription ◽

Mitochondria Dysfunction ◽

Alveolar Epithelial ◽

Ras Signaling Pathway

Abstract Backgrounds: Acute respiratory distress syndrome (ARDS) causes substantial mortality worldwide. Alveolar epithelium is one of the main sites of cell injury in ARDS. MicroRNAs (miRNAs) are small noncoding RNA molecules that are recognized as endogenous physiological regulators of gene expression. As an important miRNA, miR-145 has been studied in various diseases, while its role in ARDS remains not investigated. Methods: Intratracheal instillation of LPS was used to establish ARDS model. Cytokines from bronchoalveolar lavage fluid (BALF), lung wet/dry ratio as well as the pathological structures using H&E staining and Transmission electron microscope (TEM) was evaluated; lung miR-145 mRNA expression was detected using qPCR. And further bioinformatics was focused on the target genes and possible pathways of the gene regulation. Results: A rat model of LPS-induced ARDS was well established by intratracheal instillation of LPS. miR-145 was down-regulated in LPS-induced ARDS lung, and mitochondria dysfunction was observed in alveolar epithelial cells in ARDS lung, most obviously at 72h after LPS. TargetScan and MirDB were used to predict the target genes of miR-145, a total of 428 overlapping genes were identified, among which, 7 genes were associated with mitochondria function. The KEGG pathways were significantly enriched in MAPK signaling pathway and RAS signaling pathway, and the GO biological process terms were mainly enriched in gene binding, signal transduction, and regulation of transcription. Conclusions: The current work provided evidence between miR-145 and LPS-induced ARDS. Clearly, miR-145 was down-regulated in LPS induced lung injury, and resultant had impact on its downstream genes targeting mitochondria functions through MAPK and RAS signaling pathway.

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Effects of keratinocyte-derived and fibroblast-derived exosomes on human epidermal melanocytes

Indian Journal of Dermatology Venereology and Leprology ◽

10.25259/ijdvl_1087_19 ◽

2021 ◽

Vol 0 ◽

pp. 1-10

Author(s):

Hai-Xia Shi ◽

Ru-Zhi Zhang ◽

Li Xiao ◽

Li Wang

Keyword(s):

Signaling Pathway ◽

High Throughput ◽

High Throughput Sequencing ◽

Target Genes ◽

Tyrosinase Activity ◽

The Other ◽

Differentially Expressed ◽

Ras Signaling ◽

Sequencing Analysis ◽

Melanin Synthesis

Background: Exosomes have been demonstrated to carry proteins, membrane lipids, mRNAs and microRNAs which can be transferred to surrounding cells and regulate the functions of those recipient cells. Objectives: The objective of the study was to investigate the effects of exosomes released by keratinocytes and fibroblasts on the proliferation, tyrosinase activity and melanogenesis of melanocytes. Methods: Melanocytes, keratinocytes and fibroblasts obtained from human foreskin were cultured and exosomes secreted by keratinocytes and fibroblasts were harvested from the culture supernatants by ultracentrifugation. Each exosome fraction was divided into two parts; one part was subjected to high-throughput sequencing using an Illumina HiSeq sequencer to characterize the microRNA expression profiles, while the other part was labeled with the fluorescent dye PKH67 and was then co-cultivated with epidermal melanocytes. Results: High-throughput sequencing analysis showed 168 differentially expressed microRNA within exosomes derived from keratinocytes and from fibroblasts, 97 of those being up-regulated with the other 71 down-regulated. Gene ontology analysis showed that the target genes responsible for these differentially expressed microRNAs were mainly enriched in the protein-binding region of molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that target genes regulated by differentially expressed microRNA were mainly involved in mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, cAMP signaling pathway and Wnt signaling pathway. Keratinocyte-derived exosomes were taken up by melanocytes co-cultured with them and promoted the proliferation, tyrosinase activity and melanin synthesis of those melanocytes. However, fibroblast-derived exosomes had no similar effects on melanocytes. Conclusion: Keratinocyte-derived exosomes but not fibroblast-derived exosomes were taken up by melanocytes in co-culture and significantly stimulated their proliferation, tyrosinase activity and melanin synthesis. Those different effects may be mainly due to the differential expression of microRNAs in exosomes derived from the different types of cells. Limitations: Electron microscopy of the obtained exosomes and in-depth study of apparently differentially expressed microRNAs were not performed.

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miR-98-5p as a Novel Biomarker Suppress Liver Fibrosis by Targeting TGFβ Receptor 1

10.21203/rs.3.rs-520986/v1 ◽

2021 ◽

Author(s):

Yanhua Ma ◽

xiaoxue yuan ◽

Ming Han ◽

Kai Han ◽

Pu Liang ◽

...

Keyword(s):

Liver Fibrosis ◽

Signaling Pathway ◽

Target Genes ◽

Enrichment Analysis ◽

Hbv Infection ◽

Differentially Expressed ◽

Control Group ◽

Chronic Hbv Infection ◽

Differentially Expressed Mirnas ◽

Chronic Hbv

Abstract Hepatic fibrosis is the repair reaction of excessive deposition and abnormal distribution of extracellular matrix after various liver injuries, especially chronic HBV infection, which is a key step in the development of various chronic liver diseases to cirrhosis. Recent studies show that microRNAs (miRNA) can regulate a series of liver fibrosis-related gene express and play an important role in the development of liver fibrosis. To detect the miRNAs expression profiling and to screen the differentially expressed miRNAs in patients with HBV-related liver fibrosis, the whole blood was collected from the HBV-related liver fibrosis patients (F2/3, n=10) based on Scheuer’s staging criteria. In addition, healthy volunteers (n=8) served as the control group. The expression of plasma miRNAs was detected by IlluminaHiSeq sequencing. Cluster analysis and target genes prediction of differentially expressed miRNAs were carried out. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis of differentially expressed miRNAs target genes were performed. Compared with the healthy control group 104 miRNAs were screened out from the liver fibrosis group, among which 72 miRNAs were up-regulated and 32 were down-regulated. Pathway annotations for the target genes of the miRNAs identified were found that it participated in many signal pathways including MAPK signaling pathway, TNF signaling pathway, Notch signaling pathway, phosphatidylinositol signal system and so on. According to the bioinformatic analysis，miR-98-5p were selected for function research among the differentially expressed miRNAs.MiR-98-5p prevents liver fibrosis by targeting TGFβR1 and blocking TGFβ1/Smad3 signaling pathway. In addition, serum miR-98-5p levels were measured from a total of 70 recruited patients with chronic HBV infection and 29 healthy individuals as controls. We found that serum miR-98-5p level was significantly lower in patients with live fibrosis than in healthy controls and HBV carriers (P<0.05). Those results suggest that miR-98-5p could be a potential therapeutic target for liver fibrosis .

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Enrichment and verification of differentially expressed miRNAs in the ovarian tissue of Leizhou black ducks

10.21203/rs.3.rs-898455/v1 ◽

2021 ◽

Author(s):

Lili Lu ◽

Collins Amponsah Asiamah ◽

yuanbo Liu ◽

Rungen Ye ◽

Yiting Pan ◽

...

Keyword(s):

Signaling Pathway ◽

Egg Production ◽

Target Genes ◽

Ovarian Tissue ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Signal Pathways ◽

Laying Performance ◽

Differentially Expressed Mirnas ◽

Mirna Library

Abstract Background Ovary is an important reproductive organ for poultry. MicroRNA (miRNA) is a highly conserved class of small non-coding RNA that function in a specific manner to post-transcriptionally regulate gene expression in organisms. Currently, miRNA has been studied extensively but research on duck ovarian tissue is relatively rare. Thus, in this study, we performed the first miRNA analysis of ovarian tissues in Leizhou black ducks with low and high rates of egg production. Method: Using high-throughput sequencing technology, miRNA library was constructed to obtain miRNA expression profile; differentially expressed miRNAs were screened, to predict miRNA target genes. Results A total of 29 differentially expressed miRNAs were obtained from the miRNA library, of which 7 were up-regulated and 22 were down-regulated. Verification of 12 randomly selected miRNAs, using RT-qPCR technology showed the results are consistent with the sequencing data, indicating that the sequencing results are reliable. The GO enrichment and KEGG pathway enrichment analysis of differential miRNAs showed that target genes were significantly enriched in signal pathways related to ovarian development, such as the oxytocin signaling pathway, GnRH signaling pathway, progesterone-mediated oocyte maturation, and AMPK signal pathway. Conclusion The research results enrich the data resources of duck miRNAs, and provide a theoretical basis for further research on the laying performance of poultry and molecular-assisted breeding of poultry in the future.

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Construction and Bioinformatics Analysis of the miRNA-mRNA Regulatory Network in Diabetic Nephropathy

Journal of Healthcare Engineering ◽

10.1155/2021/8161701 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Yameng Li ◽

Yukun Xu ◽

Yawei Hou ◽

Rui Li

Keyword(s):

Diabetic Nephropathy ◽

Regulatory Network ◽

Target Genes ◽

Differentially Expressed ◽

Ras Signaling ◽

Regulatory Relationship ◽

Downstream Target ◽

Differentially Expressed Mirnas ◽

Candidate Target ◽

Geo Database

Background. MicroRNA (miRNA) has been confirmed to be involved in the occurrence, development, and prevention of diabetic nephropathy (DN), but its mechanism of action is still unclear. Objective. With the help of the GEO database, bioinformatics methods are used to explore the miRNA-mRNA regulatory relationship pairs related to diabetic nephropathy and explain their potential mechanisms of action. Methods. The DN-related miRNA microarray dataset (GSE51674) and mRNA expression dataset (GSE30122) are downloaded through the GEO database, online analysis tool GEO2R is used for data differential expression analysis, TargetScan, miRTarBase, and miRDB databases are used to predict potential downstream target genes regulated by differentially expressed miRNAs, and intersection with differential genes is used to obtain candidate target genes. According to the regulatory relationship between miRNA and mRNA, the miRNA-mRNA relationship pair is clarified, and the miRNA-mRNA regulatory network is constructed using Cytoscape. DAVID is used to perform GO function enrichment analysis and KEGG pathway analysis of candidate target genes. By GeneMANIA prediction of miRNA target genes and coexpressed genes, the protein interaction network is constructed. Results and Conclusions. A total of 67 differentially expressed miRNAs were screened in the experiment, of which 42 were upregulated and 25 were downregulated; a total of 448 differentially expressed mRNAs were screened, of which 93 were upregulated and 355 were downregulated. Using TargetScan, miRTarBase, and miRDB databases to predict downstream targets of differentially expressed miRNAs, 2283 downstream target genes coexisting in 3 databases were predicted to intersect with differentially expressed mRNAs to obtain 96 candidate target genes. Finally, 44 miRNA-mRNA relationship pairs consisting of 12 differentially expressed miRNAs and 27 differentially expressed mRNAs were screened out; further analysis showed that miRNA regulatory network genes may participate in the occurrence and development of diabetic nephropathy through PI3K/Akt, ECM-receptor interaction pathway, and RAS signaling pathway.

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miR-98-5p as a Novel Biomarker Suppress Liver Fibrosis by Targeting TGFβ Receptor 1

10.21203/rs.3.rs-520986/v2 ◽

2021 ◽

Author(s):

Yanhua Ma ◽

xiaoxue yuan ◽

Ming Han ◽

Kai Han ◽

Pu Liang ◽

...

Keyword(s):

Liver Fibrosis ◽

Signaling Pathway ◽

Target Genes ◽

Enrichment Analysis ◽

Hbv Infection ◽

Differentially Expressed ◽

Control Group ◽

Chronic Hbv Infection ◽

Differentially Expressed Mirnas ◽

Chronic Hbv

Abstract Hepatic fibrosis is the repair reaction of excessive deposition and abnormal distribution of extracellular matrix after various liver injuries, especially chronic HBV infection, which is a key step in the development of various chronic liver diseases to cirrhosis. Recent studies show that microRNAs (miRNAs) can regulate a series of liver fibrosis-related gene express and play an important role in the development of liver fibrosis. To detect the miRNAs expression profiling and to screen the differentially expressed miRNAs in patients with HBV-related liver fibrosis, the whole blood was collected from the HBV-related liver fibrosis patients (S2/3, n=8) based on Scheuer’s staging criteria. In addition, healthy volunteers(n=7) served as the control group. The expression of plasma miRNAs was detected by IlluminaHiSeq sequencing. Cluster analysis and target genes prediction of differentially expressed miRNAs were performed. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis of differentially expressed miRNAs target genes were performed. Compared with the healthy control group 77 miRNAs were screened out from the liver fibrosis group, among which 51 miRNAs were up-regulated and 26 miRNAs were down-regulated. Pathway annotations for the target genes of the miRNAs identified were found that it participated in many signal pathways including MAPK signaling pathway, TNF signaling pathway, Notch signaling pathway, phosphatidylinositol signal system and so on. According to the bioinformatic analysis, miR-98-5p were selected for function research among the differentially expressed miRNAs.MiR-98-5p prevents liver fibrosis by targeting TGFβR1 and blocking TGF β1/Smad3 signaling pathway. In addition, serum miR-98-5p levels were measured from a total of 70 recruited patients with chronic HBV infection and 29 healthy individuals as controls. We found that serum miR-98-5p level was significantly lower in patients with live fibrosis than in healthy controls and HBV carriers (P<0.05). Those results suggest that miR-98-5p could be a potential therapeutic target for liver fibrosis.

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