Co-Expression Network Analysis of Micro-RNAs and Proteins in the Alzheimer’s Brain: A Systematic Review of Studies in the Last 10 Years

MicroRNAs (miRNAs) are small non-coding nucleic acids that can regulate post-transcriptional gene expression by binding to complementary sequences of target mRNA. Evidence showed that dysregulated miRNA expression may be associated with neurological conditions such as Alzheimer’s disease (AD). In this study, we combined the results of two independent systematic reviews aiming to unveil the co-expression network of miRNAs and proteins in brain tissues of AD patients. Twenty-eight studies including a total of 113 differentially expressed miRNAs (53 of them validated by qRT-PCR), and 26 studies including a total of 196 proteins differentially expressed in AD brains compared to healthy age matched controls were selected. Pathways analyses were performed on the results of the two reviews and 39 common pathways were identified. A further bioinformatic analysis was performed to match miRNA and protein targets with an inverse relation. This revealed 249 inverse relationships in 28 common pathways, representing new potential targets for therapeutic intervention. A meta-analysis, whenever possible, revealed miR-132-3p and miR-16 as consistently downregulated in late-stage AD across the literature. While no inverse relationships between miR-132-3p and proteins were found, miR-16′s inverse relationship with CLOCK proteins in the circadian rhythm pathway is discussed and therapeutic targets are proposed. The most significant miRNA dysregulated pathway highlighted in this review was the hippo signaling pathway with p = 1.66 × 10−9. Our study has revealed new mechanisms for AD pathogenesis and this is discussed along with opportunities to develop novel miRNA-based drugs to target these pathways.

Download Full-text

Characteristic Dissection of Xanthomonas oryzae pv. oryzae Responsive MicroRNAs in Rice

International Journal of Molecular Sciences ◽

10.3390/ijms21030785 ◽

2020 ◽

Vol 21 (3) ◽

pp. 785

Author(s):

Yanfeng Jia ◽

Chunrong Li ◽

Quanlin Li ◽

Pengcheng Liu ◽

Dongfeng Liu ◽

...

Keyword(s):

Rice Variety ◽

Bioinformatic Analysis ◽

Infection Process ◽

Xanthomonas Oryzae ◽

Differentially Expressed ◽

Small Rna Sequencing ◽

Sequencing Data ◽

Stem Loop ◽

Differentially Expressed Mirnas ◽

Plant Pathogen Interaction

MicroRNAs (miRNAs) are crucial player in plant-pathogen interaction. While the evidence has demonstrated that rice miRNAs mediate immune response to pathogens invasion, the roles of miRNAs on Xanthomonas oryzae pv. oryzae (Xoo) attack remain be in place. Herein, we monitored the responsive changes of rice miRNAs at 0, 8, 24 h across Xoo strain PXO86 infection in its compatible rice variety IR24 and incompatible variety IRBB5 by small RNA sequencing, and the genes targeted by miRNAs were also detected via degradome technology. The faithfulness of sequencing data was validated through quantitative real-time stem-loop reverse transcription-polymerase chain reaction assay. Bioinformatic analysis showed that the differentially expressed miRNAs could be divided into three immunity-related clusters, and 80 regulatory units were emerged in infection process, which comprises 29 differentially expressed known miRNAs and 38 cleaved targets. Furthermore, the miRNA presumptive function of separate immunity cluster in rice-Xoo interplay was confirmed through overexpressing osa-miR164a, osa-miR167d and osa-miR159b, and the disruption of regulatory units, osa-miR164a/OsNAC60, osa-miR167d-5p/OsWD40-174 and osa-miR159b/OsMYBGA, OsLRR-RLK2, OsMPK20-4, may reset rice defense response to Xoo infestation in a controllable manner. These findings provide new insights into the complex roles of characteristic miRNAs and their targets in rice-Xoo interactions.

Download Full-text

Inhibition of miR-141 and miR-200a Increase DLC-1 and ZEB2 Expression, Enhance Migration and Invasion in Metastatic Serous Ovarian Cancer

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17082766 ◽

2020 ◽

Vol 17 (8) ◽

pp. 2766 ◽

Cited By ~ 2

Author(s):

Norhazlina Abdul Wahab ◽

Zahreena Othman ◽

Noor Wahidah Mohd Nasri ◽

Mohd Helmy Mokhtar ◽

Siti Fatimah Ibrahim ◽

...

Keyword(s):

Ovarian Cancer ◽

Differentially Expressed ◽

Locked Nucleic Acid ◽

Migration And Invasion ◽

Serous Ovarian Cancer ◽

Novel Mirna ◽

Ovarian Carcinogenesis ◽

Differentially Expressed Mirnas

The role of microRNA (miRNA) in ovarian cancer has been extensively studied as a regulator for its targeted genes. However, its specific role in metastatic serous ovarian cancer (SOC) is yet to be explored. This paper aims to investigate the differentially expressed miRNAs in metastatic SOC compared to normal. Locked nucleic acid PCR was performed to profile miRNA expression in 11 snap frozen metastatic SOC and 13 normal ovarian tissues. Functional analysis and regulation of their targeted genes were assessed in vitro. Forty-eight miRNAs were significantly differentially expressed in metastatic SOC as compared to normal. MiR-19a is a novel miRNA to be upregulated in metastatic SOC compared to normal. DLC1 is possibly regulated by miR-141 in SOC. MiR-141 inhibition led to significantly reduced cell viability. Cell migration and invasion were significantly increased following miRNA inhibition. This study showed the aberrantly expressed miRNAs in metastatic SOC and the roles of miRNAs in the regulation of their targeted genes and ovarian carcinogenesis.

Download Full-text

MicroRNA-126-5p Inhibits the Migration of Breast Cancer Cells by Directly Targeting CNOT7

Technology in Cancer Research & Treatment ◽

10.1177/1533033820977545 ◽

2020 ◽

Vol 19 ◽

pp. 153303382097754

Author(s):

Yuying Miao ◽

Jiang Lu ◽

Baozhen Fan ◽

Lecan Sun

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Mcf7 Cell ◽

Bioinformatic Analysis ◽

Negative Control ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Differentially Expressed Mirnas ◽

Mcf7 Cell Line ◽

Breast Cancer Mcf7 Cell

Background: To assess the effect of microRNA-126-5p (miR-126-5p) on the migration of the breast cancer MCF7 cell line. Methods: GSE143564 was downloaded from the Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo ) to identify the differentially expressed miRNAs between breast cancer and adjacent tissues. Quantitative reverse transcription PCR (RT-qPCR) was used to assess miR-126-5p levels in the normal 184A1 breast cell line and the breast cancer MCF7 cell line. The MCF7 cell line was then transfected with miR-126-5p mimics or corresponding negative control (NC-mimic). The proliferation and migration abilities of the MCF7 cell line were measured by methyl thiazolyl tetrazolium (MTT), Transwell and scratch healing assays. CCR4-NOT transcription complex and subunit 7 (CNOT7) expression levels in the NC-mimic and miR-126-5p mimic groups were measured by Western blot analysis. Bioinformatic analysis and a dual-luciferase reporter assay were performed to identify the miR-126-5p target gene. Results: One hundred forty-eight differentially expressed miRNAs (downregulated = 55, upregulated = 93) were identified. MiR-126-5p expression in the MCF7 cell line was significantly downregulated relative to that of 184A1 cell line (P < 0.05). Compared with that observed in the control and NC-mimic groups, cell proliferation in the miR-126-5p mimic group was significantly decreased at 48 and 72 h posttransfection (P < 0.05). In addition, the scratch healing rate and number of membrane-piercing cells in the miR-126-5p overexpression group were lower than those detected in the control and NC groups (P < 0.05). Furthermore, miR-126-5p could reduce the luciferase activity for the wild-type CNOT7 gene 3’-untranslated region (UTR) reporter (P < 0.05) but had no effect on the mutant 3’UTR reporter (P > 0.05). Compared with that observed in the NC and control groups, the levels of CNOT7 in the miR-126-5p overexpression group decreased (P < 0.05). Conclusion: Upregulation of miR-126-5p can inhibit the migration of the breast cancer MCF7 cell line, which may involve its direct targeting of the 3’UTR of CNOT7.

Download Full-text

Integrated transcriptome and miRNA analysis uncovers molecular regulators of aerial stem-to-rhizome transition in the medical herb Gynostemma pentaphyllum

BMC Genomics ◽

10.1186/s12864-019-6250-8 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Qi Yang ◽

Shibiao Liu ◽

Xiaoning Han ◽

Jingyi Ma ◽

Wenhong Deng ◽

...

Keyword(s):

Expression Patterns ◽

Growth Inhibitor ◽

Differentially Expressed ◽

Developmental Phase ◽

Sequencing Data ◽

Gynostemma Pentaphyllum ◽

Novel Mirna ◽

The Family ◽

Differentially Expressed Mirnas ◽

Aerial Stem

Abstract Background Gynostemma pentaphyllum is an important perennial medicinal herb belonging to the family Cucurbitaceae. Aerial stem-to-rhizome transition before entering the winter is an adaptive regenerative strategy in G. pentaphyllum that enables it to survive during winter. However, the molecular regulation of aerial stem-to-rhizome transition is unknown in plants. Here, integrated transcriptome and miRNA analysis was conducted to investigate the regulatory network of stem-to-rhizome transition. Results Nine transcriptome libraries prepared from stem/rhizome samples collected at three stages of developmental stem-to-rhizome transition were sequenced and a total of 5428 differentially expressed genes (DEGs) were identified. DEGs associated with gravitropism, cell wall biosynthesis, photoperiod, hormone signaling, and carbohydrate metabolism were found to regulate stem-to-rhizome transition. Nine small RNA libraries were parallelly sequenced, and seven significantly differentially expressed miRNAs (DEMs) were identified, including four known and three novel miRNAs. The seven DEMs targeted 123 mRNAs, and six pairs of miRNA-target showed significantly opposite expression trends. The GpmiR166b-GpECH2 module involved in stem-to-rhizome transition probably promotes cell expansion by IBA-to-IAA conversion, and the GpmiR166e-GpSGT-like module probably protects IAA from degradation, thereby promoting rhizome formation. GpmiR156a was found to be involved in stem-to-rhizome transition by inhibiting the expression of GpSPL13A/GpSPL6, which are believed to negatively regulate vegetative phase transition. GpmiR156a and a novel miRNA Co.47071 co-repressed the expression of growth inhibitor GpRAV-like during stem-to-rhizome transition. These miRNAs and their targets were first reported to be involved in the formation of rhizomes. In this study, the expression patterns of DEGs, DEMs and their targets were further validated by quantitative real-time PCR, supporting the reliability of sequencing data. Conclusions Our study revealed a comprehensive molecular network regulating the transition of aerial stem to rhizome in G. pentaphyllum. These results broaden our understanding of developmental phase transitions in plants.

Download Full-text

Identifying Differentially Expressed MicroRNAs Between Cirrhotic and Non-Cirrhotic Hepatocellular Carcinoma and Exploring Their Functions Using Bioinformatic Analysis

Cellular Physiology and Biochemistry ◽

10.1159/000492254 ◽

2018 ◽

Vol 48 (4) ◽

pp. 1443-1456 ◽

Cited By ~ 6

Author(s):

Ying Mei ◽

Yu You ◽

Jin Xia ◽

Jian-Ping Gong ◽

Yun-Bing Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Bioinformatic Analysis ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Online Tools ◽

Tumor Stages ◽

Differentially Expressed Mirnas ◽

Cancer Genome Atlas ◽

Cirrhotic Patients ◽

Independent Risk Factors

Background/Aims: Few studies have been designed to directly investigate the exact mechanisms underlying the different phenotypes between cirrhotic and non-cirrhotic hepatocellular carcinoma (HCC). This study aimed to illuminate the incidence and developmental mechanisms for both types of HCC through differentially expressed microRNAs (miRNAs) using bioinformatic analysis. Methods: The miRNA-seq data and clinical data of patients (from The Cancer Genome Atlas (TCGA) database) were utilized to determine differentially expressed miRNAs between cirrhotic and non-cirrhotic HCC. Afterwards, the function of the selected miRNAs was predicted with online tools. Furthermore, the miRNA expression and clinical significance were validated by external datasets and our experiment. Results: The present study included 135 non-cirrhotic and 80 cirrhotic patients to find differentially expressed miRNAs. Among them, four miRNAs (mir-1296, mir-23c, mir-149, and mir-95) were finally selected for further validation and analysis. Correlation analysis found that two miRNAs are greatly associated with the non-cirrhotic HCC patients’ clinical traits, such as the T, M, and N tumor stages. However, only mir-23c was associated with the cirrhotic HCC patients’ tumor T and N stages. Furthermore, survival analysis revealed that increased mir-149 in non-cirrhotic HCC, patients’ age and the existence of vessels in the tumor in cirrhotic HCC were independent risk factors for the patients’ postoperative overall survival. Functional and interaction analyses also supported the notion that these miRNAs function through some pathways that influence the behavior of the HCC. These results are strongly supported by analysis of extra datasets and our experiment. Conclusions: The cirrhotic and non-cirrhotic HCC types involve differentially expressed miRNAs, which are correlated with distinctive pathological traits. To some extent, non-cirrhotic HCC seems more dependent on miRNA network regulation, but additional studies are needed to confirm this conclusion.

Download Full-text

Bioinformatics Analysis of Key micro-RNAs and mRNAs under the Hand, Foot, and Mouth Disease Virus Infection

Polish Journal of Microbiology ◽

10.33073/pjm-2020-052 ◽

2020 ◽

Vol 69 (4) ◽

pp. 479-490

Author(s):

SHENG LIN ◽

LIU YANG ◽

SHIBIAO WANG ◽

BIN WENG ◽

MIN LIN

Keyword(s):

Virus Infection ◽

Bioinformatics Analysis ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Differentially Expressed ◽

Micro Rnas ◽

Mouth Disease Virus ◽

Differentially Expressed Mirnas ◽

Foot And Mouth ◽

Go Terms

To clarify crucial key micro-RNAs and mRNAs associated with hand, foot, and mouth disease (HFMD) virus infection, we conducted this bioinformatics analysis from four GEO datasets. The following datasets were used for the analysis: GSE85829, GSE94551, GSE52780, and GSE45589. Differentially expressed genes (DEGs) were acquired, and the analysis of functional and pathway enrichment and the relative regulatory network were conducted. After screening common differentially expressed miRNAs (DE-miRNAs), five key miRNAs were acquired: miR-100-3p, miR-125a-3p, miR-1273g-3p, miR-5585-3p, and miR-671-5p. There were three common enriched GO terms between miRNA-derived prediction and mRNA-derived analysis: biosynthetic process, cytosol, and nucleoplasm. There was one common KEGG pathway, i.e., cell cycle shared between miRNA-based and mRNA-based enrichment. Using TarBase V8 in DIANA tools, we acquired 1,520 potential targets (mRNA) from the five key DE-miRNAs, among which the159 DE-mRNAs also included 11 DEGs. These common DEGs showed a PPI network mainly connected by SMC1A, SMARCC1, SF3B3, LIG1, and BRMS1L. Together, changes in five key miRNAs and 11 key mRNAs may play crucial roles in HFMD progression. A combination of these roles may benefit the early diagnosis and treatment of HFMD.

Download Full-text

Identification and validation of key long non-coding RNAs in resveratrol protect against IL-1β-treated chondrocytes via integrated bioinformatic analysis

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02574-4 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Hong Yi ◽

Wei Zhang ◽

Sheng-Yu Cui ◽

Jian-Bo Fan ◽

Xin-Hui Zhu ◽

...

Keyword(s):

Signaling Pathway ◽

High Throughput Sequencing ◽

Bioinformatic Analysis ◽

Differentially Expressed ◽

Venn Diagram ◽

Skin Development ◽

Differentially Expressed Mirnas ◽

Single Fertilization ◽

Non Coding Rnas ◽

First Time

Abstract Background Long non-coding RNAs (lncRNAs) participate in regulation of gene transcription, but little is known about the correlation among resveratrol and lncRNAs. This study aimed to identify and validate the key lncRNAs in resveratrol protect against IL-1β-treated chondrocytes. Methods In this experiment, high-throughput sequencing technique was performed to identify the differentially expressed lncRNAs, miRNAs, and mRNAs between IL-1β-treated chondrocytes with or not resveratrol. Moreover, gene ontology and KEGG pathway of the differentially expressed genes were carried out by R software. Then, lncRNA-miRNA-mRNA network was constructed by Cytoscape software. Venn diagram was performed to identify the potentially target miRNAs of LINC00654. Then, real-time polymerase chain reaction (RT-PCR) was performed to validate the most significantly differentially expressed lncRNAs. Results Totally, 1016 differentially expressed lncRNAs were identified (493 downregulated) between control and resveratrol-treated chondrocytes. Totally, 75 differentially expressed miRNAs were identified (downregulated = 54, upregulated = 21). Totally, 3308 differentially expressed miRNAs were identified (downregulated = 1715, upregulated = 1593). GO (up) were as follows: skin development, response to organophosphorus. GO (down) mainly included visual perception, single fertilization, and sensory perception of smell. KEGG (up) were as follows: TNF signaling pathway and TGF-beta signaling pathway. KEGG (down) were as follows: viral protein interaction with cytokine and cytokine receptor. We identified that LINC00654 and OGFRL1 were upregulated in resveratrol-treated chondrocytes. However, miR-210-5p was downregulated in resveratrol-treated chondrocytes. Conclusion In sum, the present study for the first time detected the differential expressed lncRNAs involved in resveratrol-treated chondrocytes via employing bioinformatic methods.

Download Full-text

Serum tRNA-Derived Fragments as Potential Biomarkers in Children with Acute Intussusception

10.21203/rs.3.rs-50064/v1 ◽

2020 ◽

Author(s):

Wei Chen ◽

Lian Zhao ◽

Wan-liang Guo

Keyword(s):

High Throughput Sequencing ◽

Predictive Accuracy ◽

Predictive Biomarker ◽

Differentially Expressed ◽

Roc Curve Analysis ◽

Potential Biomarker ◽

Micro Rnas ◽

Differentially Expressed Mirnas ◽

Upregulated Genes ◽

Selection Of

Abstract Background: The aim of the present study was to investigate whether transfer ribonucleic acid (tRNA)–derived fragments (tRFs) can serve as candidate biomarkers for pediatric intussusception.Methods: Using high-throughput sequencing technology, we identified differentially expressed tRFs, and ultimately selected three tRFs to establish a signature as a predictive biomarker of pediatric intussusception. Selection of these three upregulated genes was veriﬁed using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). We conducted receiver operator characteristic (ROC) curve analysis to evaluate the predictive accuracy of the selected genes for pediatric intussusception.Results: We detected 732 tRFs and tRNA-derived stress-induced RNA (tiRNAs), 1705 micro-RNAs (miRNAs), 52 differentially expressed miRNAs, and 34 differentially expressed tRFs and tiRNAs between patients and controls. Compared with controls, we found 33 upregulated miRNAs, 24 upregulated tRFs and tiRNAs, 19 downregulated miRNAs, and 10 downregulated tRFs and tiRNAs in children with intussusception. Using qPCR, the expression trends of tRF-Leu-TAA-006, tRF-Gln-TTG-033 and tRF-Lys-TTT-028 were consistent with the sequencing results. AUCs of tRF-Leu-TAA-006, tRF-Gln-TTG-033 and tRF-Lys-TTT-028 were 0.984, 0.970 and 0.837, respectively.Conclusion: Circulating tRF-Leu-TAA-006, tRF-Gln-TTG-033 and tRF-Lys-TTT-028 expression might be a novel potential biomarker for diagnosis of pediatric intussusception.

Download Full-text

Systematic assessment of commercially available low-input miRNA library preparation kits

10.1101/702456 ◽

2019 ◽

Cited By ~ 1

Author(s):

Fatima Heinicke ◽

Xiangfu Zhong ◽

Manuela Zucknick ◽

Johannes Breidenbach ◽

Arvind Sundaram ◽

...

Keyword(s):

High Throughput Sequencing ◽

Differentially Expressed ◽

Detection Sensitivity ◽

Library Preparation ◽

Experimental Conditions ◽

Total Rna ◽

Systematic Assessment ◽

Micro Rnas ◽

Differentially Expressed Mirnas ◽

Commercial Kits

AbstractHigh-throughput sequencing is increasingly favoured to assay the presence and abundance of micro RNAs (miRNAs) in biological samples, even from low RNA amounts, and a number of commercial vendors now offer kits that allow miRNA sequencing from sub-nanogram (ng) inputs. However, although biases introduced during library preparation have been documented, the relative performance of current reagent kits has not been investigated in detail. Here, six commercial kits capable of handling <100ng total RNA input were used for library preparation, performed by kit manufactures, on synthetic miRNAs of known quantities and human biological total RNA samples. We compared the performance of miRNA detection sensitivity, reliability, titration response and the ability to detect differentially expressed miRNAs. In addition, we assessed the use of unique molecular identifiers sequence (UMI) tags in one kit. We observed differences in detection sensitivity and ability to identify differentially expressed miRNAs between the kits, but none were able to detect the full repertoire of expected miRNAs. The reliability within the replicates of all kits was good, while larger differences were observed between the kits, although none could accurately quantify the majority of miRNAs. UMI tags, at least within the input ranges tested, offered little advantage to improve data utility. In conclusion, biases in miRNA abundance are heavily influenced by the kit used for library preparation, suggesting that comparisons of datasets prepared by different procedures should be made with caution. This article is intended to assist researchers select the most appropriate kit for their experimental conditions.

Download Full-text