ABSTRACT
Osteoporosis （OP） is a skeletal metabolic disease characterized by bone loss and destruction of bone microstructure. Changes in estrogen levels are not the only pathogenic factors for the occurrence and development of OP. MicroRNA （miRNA） plays an important regulatory role in cells. The complementary sequences of miRNA and targeted mRNA combine to inhibit the expression of targeted mRNA through post-transcriptional regulation， forming a complex regulatory network. Research suggests that miRNA is closely related to the occurrence and development of various diseases， including inflammatory diseases， metabolic diseases， and cancer. Targeted mRNA participates in post-transcriptional gene expression regulation in OP， mainly regulating the balance among bone construction， bone resorption， and osteoblast differentiation. Therefore， miRNA-based gene therapy is a rapidly developing disease treatment strategy. Traditional Chinese medicine can improve bone metabolism by intervening in miRNA differential expression to target and regulate osteogenic/osteoclast differentiation. This article summarized the targeting effects of miRNAs in physiological and developmental processes such as bone cell proliferation， differentiation， survival， and apoptosis， reviewed and classified their mechanisms of action and targets， and sorted out the current treatment methods of traditional Chinese medicine for preventing and treating OP and drugs that exert bone protective functions through miRNAs. This review is expected to provide theoretical reference and research guidance for future research on OP treatment by regulating miRNA.
ABSTRACT
Pulpitis and periapical inflammation are two common diseases in stomatology today. Existing treatment options primarily include root canal therapy and pulp revascularization, which can effectively control inflammation and preserve the affected tooth while also causing permanent deactivation of the pulp tissue, structural failure, and secondary infection. In recent years, research on dental pulp regeneration has progressively entered the public consciousness because of tissue engineering technology that combines stem cells and biomaterials. Due to their multi⁃differentiation and high proliferation, dental pulp stem cells (DPSCs) isolated from permanent or deciduous teeth have emerged as a significant stem cell source for dentin or pulp tissue regeneration. However, the number and survival time of live cells in the dam⁃ aged area are impacted, which significantly limits the efficacy of stem cells since they are unable to efficiently be recruited to the injured area. The ability of DPSCs to migrate and multiply must therefore be enhanced. This study sought to determine if miR⁃31 (miR⁃31) may significantly enhance the proliferative and migratory capacities of DPSCs. The tissue block enzyme digestion method was used to successfully separate and culture DPSCs from dental pulp tissues, and the miR⁃31 levels in dental pulp tissues and DPSCs from normal and inflammatory teeth were compared. The results of real⁃time fluorescence quanti⁃ tative PCR (RT⁃qPCR) revealed that the expression level of miR⁃31 in dental pulp tissues and DPSCs from inflammatory teeth was significantly lower when compared to the control group (P<0. 05). Interfer⁃ ence and over⁃expression of miR⁃31 expressions in DPSCs were specifically divided into three groups: the NC group, the miR⁃31 agomir (over⁃expressed) group and the miR⁃31 antagomir (inhibitor) group. RTq⁃PCR results showed that the transfection was successful (P<0. 001). The results of CCK⁃8, wound⁃ healing, and Transwell migration experiments showed that overexpression of miR⁃31 successfully improved the proliferation and migration abilities of DPSCs compared with the control group (P<0. 05). Further⁃ more, Western blotting analysis revealed that miR⁃31 overexpression increased the expression of important migratory proteins, including CXC chemokine receptor type 4 (CXCR4) and matrix metalloproteinase2 (MMP2), as well as key proliferation proteins Ki67 and proliferating cell nuclear antigen (PCNA) (P< 0. 05). This study demonstrates that miR⁃31 can effectively boost the proliferation and migratory ability of DPSCs, providing strong theoretical support for the increased use of DPSCs in regenerative medicine.
ABSTRACT
ObjectiveThe aim of this study is to investigate the role of salidroside in regulating the miR-1343-3p/MAP3K6 （mitogen-activated protein kinase kinase kinase 6）/MMP24 （membrane-type matrix metalloproteinase 24） signaling pathway to inhibit gastric cancer cell proliferation and migration. MethodsHuman gastric cancer cells （MGC-803） were divided into several groups based on different salidroside concentrations： a control group （0 μmol/mL）， a low-dose group （6 μmol/mL）， a medium-dose group （12 μmol/mL）， and a high-dose group （24 μmol/mL）. The anti proliferative effects of salidroside on human gastric cancer cells were evaluated by CCK-8 assay. Clonogenic assay was used to examine the effects of salidroside drugs on the clonogenic ability of human gastric cancer cells. Transwell assay was performed to detect the effect of salidroside on the invasive ability of human gastric cancer cells. Cell scratch assay was performed to detect the effect of salidroside on the migration ability of human gastric cancer cells. The miRNA expression profile was analyzed by using RNA-seq in cancer cells for 24 h after salidroside treatment. The differentially expressed miRNAs were clustered and their target genes were predicted. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） were used to analyze and predict the functions of these target genes， and the interaction networks were established. Immunocytofluorescence was used to detect the expression of target proteins， and the transcription of candidate genes was detected by q-PCR. ResultsCCK-8 cytotoxicity experiments showed that salidroside inhibited the proliferation of MGC-803 cells （P < 0.01）. Cell cloning experiments showed that salidroside reduced the clonal formation capacity of MGC-803 cells （P < 0.000 1）. Cell invasion experiments showed that salidroside reduced the MGC-803 cell invasion capacity （P < 0.000 1）. Cell scratch experiments showed that salidroside reduced the cell migration capacity （P < 0.000 1）. RNA-seq findings showed that the expression of 44 miRNAs changed significantly after salidroside treatment in cancer cells （P < 0.05）. Bioinformatic analysis showed that there were 1 384 target mRNAs corresponding to the differentially expressed miRNAs， and the expression of the tumor suppressor miR-1343-3p was significantly upregulated after salidroside treatment （P < 0.01），and resulted in down-regulated transcription of MAP3K6 and MMP24 genes which are related to the proliferation and migration of cancer cells （P < 0.05）. Immunofluorescence experiments demonstrated that salidroside reduced protein expression levels in MAP3K6 and MMP24 genes （P < 0.000 1）. q-PCR experiments showed that salidroside reduced the mRNA expression level of MAP3K6 and MMP24 genes （P < 0.000 1）， while miRNA expression in miR-1343-3p gene was upregulated （P < 0.000 1）. ConclusionSalidroside regulates the miRNA-1343-3p/MAP3K6/MMP24 signaling molecules to inhibit proliferation and invasion of gastric cancer cells.
ABSTRACT
Non-exosomal non-coding RNAs (non-exo-ncRNAs) and exosomal ncRNAs (exo-ncRNAs) have been associated with the pathological development of myocardial infarction (MI). Accordingly, this analytical review provides an overview of current MI studies on the role of plasma non-exo/exo-ncRNAs. We summarize the features and crucial roles of ncRNAs and reveal their novel biological correlations via bioinformatics analysis. The following contributions are made: (1) we comprehensively describe the expression profile, competing endogenous RNA (ceRNA) network, and "pre-necrotic" biomarkers of non-exo/exo-ncRNAs for MI; (2) functional enrichment analysis indicates that the target genes of ncRNAs are enriched in the regulation of apoptotic signaling pathway and cellular response to chemical stress, etc.; (3) we propose an updated and comprehensive view on the mechanisms, pathophysiology, and biomarker roles of non-exo/exo-ncRNAs in MI, thereby providing a theoretical basis for the clinical management of MI.
Subject(s)
Humans , RNA, Untranslated/genetics , RNA , Myocardial Infarction/genetics , Biomarkers , Computational Biology , MicroRNAs/geneticsABSTRACT
Chinese hamster ovary (CHO) cells play an irreplaceable role in biopharmaceuticals because the cells can be adapted to grow in suspension cultures and are capable of producing high quality biologics exhibiting human-like post-translational modifications. However, gene expression regulation such as transgene silencing and epigenetic modifications may reduce the recombinant protein production due to the decrease of expression stability of CHO cells. This paper summarized the role of epigenetic modifications in CHO cells, including DNA methylation, histone modification and miRNA, as well as their effects on gene expression regulation.
Subject(s)
Cricetinae , Animals , Humans , Cricetulus , CHO Cells , Epigenesis, Genetic/genetics , DNA Methylation , Gene Expression Regulation , Recombinant Proteins/geneticsABSTRACT
@#Proliferative vitreoretinopathy(PVR)is a eye disease characterized by the formation of epiretinal membranes(ERM)composed of extracellular matrix(ECM)and various types of cells in the vitreous and/or the surface of the retina through the wound repair and fibrotic process. ERM shrinks to form retinal folds and stretches the retina to cause retinal detachment(RD). Epithelial-mesenchymal transition(EMT)of retinal pigment epithelial(RPE)cells and accumulation of ECM are considered to be the main pathological mechanisms for the formation of ERM. RPE cells undergo a process named EMT induced by transforming growth factor-β(TGF-β), by which differentiated epithelial cells go through epithelial phenotypic loss, the weakness of cell-cell contact and mesenchymal phenotype expression. Fibroblast-like cells differentiated from mesenchymal cells produce ECM and other components, which forms ERM together with glial cells and fibroblasts, <i>etc</i>. Recent studies indicated a lot of cytokines/growth factors, transcriptional factors, and microRNA(miRNA)regulate the development of EMT in RPE cells, in which miRNA is a novel and powerful regulatory gene and plays a critical regulatory role in the EMT process of PVR. This review focuses on the current understandings of the mechanism and the interventional treatments of miRNA in PVR.
ABSTRACT
Long noncoding RNAs (lncRNAs) are expressed in different species and different tissues, and perform different functions, but little is known about their involvement in the synthesis or secretion of follicle-stimulating hormone (FSH). In general, we have revealed lncRNA‒microRNA (miRNA)‒messenger RNA (mRNA) interactions that may play important roles in rat primary pituitary cells. In this study, a new lncRNA was identified for the first time. First, we analyzed the gene expression of lncRNA-m18as1 in different tissues and different stages by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and observed the localization of lncRNA-m18as1 with fluorescence in situ hybridization, which indicated that this lncRNA was distributed mainly in the cytoplasm. Next, we used RT-qPCR and enzyme-linked immunosorbent assay (ELISA) to analyze the regulation of FSH synthesis and secretion after overexpression or knockdown of lncRNA-m18as1 and found that lncRNA-m18as1 was positively correlated with FSH synthesis and secretion. In addition, mothers against decapentaplegic homolog 2 (Smad2) was highly expressed in our sequencing results. We also screened miR-18a-5p from our sequencing results as a miRNA that may bind to lncRNA-m18as1 and Smad2. We used RNA immunoprecipitation-qPCR (RIP-qPCR) and/or dual luciferase assays to confirm that lncRNA-m18as1 interacted with miR-18a-5p and miR-18a-5p interacted with Smad2. Fluorescence in situ hybridization (FISH) showed that lncRNA-m18as1 and miR-18a-5p were localized mainly in the cytoplasm. Finally, we determined the relationship among lncRNA-m18as1, miR-18a-5p, and the Smad2/3 pathway. Overall, we found that lncRNA-m18as1 acts as a molecular sponge of miR-18a-5p to regulate the synthesis and secretion of FSH through the Smad2/3 pathway.
Subject(s)
Animals , Rats , Cell Line, Tumor , Cell Proliferation , Follicle Stimulating Hormone/metabolism , Gene Expression Regulation, Neoplastic , In Situ Hybridization, Fluorescence , MicroRNAs/metabolism , RNA, Long Noncoding/metabolismABSTRACT
Type 2 diabetes mellitus (T2DM) is a metabolic disease with an increasing incidence worldwide, which leads to damage to various tissues and organs including the liver. MiR-31 is conserved across species and closely associated with metabolic diseases, but its role in type 2 diabetic liver injury has not been elucidated. This study aimed to investigate the effect of miR-31 on liver injury in type 2 diabetes and its underlying mechanism. Four to six weeks old male FVB mice and miR-31-positive transgenic mice were randomly divided into FVB mice control group (C), FVB mice induced diabetes group (DM) and miR-31-overexpression transgenic mice induced diabetes group (31DM). After 1 week of adaptive feeding, the T2DM mouse model was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ) for 6 weeks. The general condition of mice and related metabolic indicators showed that the increased food and water intake, weight loss and glucose and lipid metabolism disorders could be reversed by miR-31 in T2DM mice. HE staining and liver histological activity index (HAI) scoring results showed that miR-31 improved the inflammatory status in the liver tissue of T2DM mice and decreased the HAI score. RT-qPCR results showed that the high expression of miR-31 was accompanied by a decrease in the expression of activating transcription factor 6 (ATF6) mRNA in the liver of T2DM mice. Furthermore, Western blotting results showed that miR-31 inhibited the expression of endoplasmic reticulum stress-related proteins such as ATF6, glucoregulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the liver of T2DM mice. In conclusion, miR-31 may ameliorate liver injury in T2DM mice by regulating glucose and lipid metabolism disorders and insulin resistance, and inhibiting endoplasmic reticulum stress factors such as ATF6, GRP78, and CHOP.
ABSTRACT
Early diagnosis of cancer can significantly improve the survival rate of cancer patients, especially in patients with hepatocellular carcinoma (HCC). Machine learning is an effective tool in cancer classification. How to select high⁃classification accuracy feature subsets with low dimension in complex and high⁃dimensional cancer datasets is a difficult problem in cancer classification. In this paper, we propose a novel feature selection method, SC⁃BPSO: a two⁃stage feature selection method implemented by combining the Spearman correlation coefficient, chi⁃square independent test⁃based filter method, and binary particle swarm optimal (BPSO) based wrapper method. It has been applied to the cancer classification of high⁃dimensional data to classify normal samples and HCC samples. The dataset in this paper is obtained from 130 liver tissue microRNA sequence data (64 hepatocellular carcinoma, 66 normal liver tissue) from National Center for Bioinformatics (NCBI) and European Bioinformatics Institute (EBI). First, the liver tissue microRNA sequence data was preprocessed to extract the three types of features of microRNA expression, editing level and post⁃editing expression. Then, the parameters of the SC⁃BPSO algorithm in the liver cancer classification were adjusted to select a subset of key features. Finally, classifiers were used to establish classification models, predict the results, and compare the classification results with the feature subset selected by the information gain filter, the information gain ratio filter and the BPSO wrapper feature selection algorithm using the same classifier. Using the feature subset selected by the SC⁃BPSO algorithm, the classification accuracy is up to 98. 4%. The experimental results showed that compared with the other three feature selection algorithms, the SC⁃ BPSO algorithm can effectively find feature subsets with relatively small size and higher accuracy. This may have important implications for cancer classification with a small number of samples and high⁃ dimension features.
ABSTRACT
In this study, high-throughput sequencing technology was used to analyze the differentiallyexpressed microRNA (miRNA) of astrocyte-derived exosomes in control group and oxygen and glucosedeprivation/ reoxygenation (OGD/ R) group. Ultracentrifugation was used to extract exosomes from thesupernatant of astrocyte medium in the control group and OGD/ R group. Transmission electron microscopyshowed that exosomes had a typical vesicle shape with intact membrane and low electron content density. Nanoparticle tracking technology (NTA) detected astrocyte exosomes with a size of 100. 5 ± 31. 1 nm, accounting for 96. 8%. Western blot detection showed that the exosome contained exosome-specificproteins tumor-susceptibility protein (TSG101), heat shock protein 60 (Hsp60), ALG-2-interactingprotein X (ALIX). Compared with the control group, 41 miRNAs in the exosomes of the OGD / R groupwere significantly changed, of which 20 miRNAs were increased and 21 miRNAs were decreasedsignificantly (P < 0. 05). Gene ontology function (GO) analysis showed that significantly differentiallytarget genes were mainly involved in protein glycosylation, lipid metabolism, phosphorylation, Golgiapparatus, endoplasmic reticulum, endosome, cytoplasmic vesicles and cell protrusions, etc. KyotoEncyclopedia of Genes and Genomes (KEGG) pathway analysis found that differential miRNAs weremainly related to metabolic pathways and signaling pathways such as butyrate metabolism, ß-alaninemetabolism, fatty acid degradation, mitophagy and P53 signaling pathway. Sequencing analysis of theexosomal miRNAs derived from control and OGD / R astrocytes and target gene function enrichmentanalysis can be useful for the mechanism study of astrocyte exosomes in response to oxygen and glucosedeprivation reperfusion.
ABSTRACT
Endoplasmic reticulum stress (ERS) is a cellular defensive response to restore homeostasisand reduce the protein load. Over-activation of ERS can induce cell differentiation, proliferation, apoptosis, and autophagy. MicroRNAs (miRNAs) are endogenous non-coding RNAs (ncRNAs) thatregulate the expression of key proteins and genes in the ERS signaling pathway through post-transcriptional action. Meanwhile, activated ERS signaling pathway can indirectly regulate the expressionand function of target genes by decreasing miRNA stability. Based on a brief introduction of ERS classicalsignaling pathways, this paper further elaborated how microRNAs regulate ERS signaling pathways topromote apoptosis and proliferation, and what effect they would have on the expression profile of diseasesbased on this association. We also summarize the regulation of ERS on miRNAs expression and thecurrent research status. The mutual regulation between the two could provide a new idea for the follow-upresearch on the therapeutic targets of diseases.
ABSTRACT
Macrophage polarization is a process of phenotypic regulation based on the surroundingstimulus environment, which is generally polarized into two phenotypes, namely classical activated M1macrophages and alternative activated M2 macrophages. In short, M1 macrophages are characterized aspro-inflammatory and anti-tumor; M2 macrophages are anti-inflammatory and pro-tumor. Macrophagepolarization is considered to be a key regulator of human physiology and pathology processes, and itseffectiveness depends on the coordinated expression of key factors, whose expression is finely regulated bymicroRNAs (miRNAs) at the post-transcriptional level. MicroRNAs are small non-coding RNAs that havethe ability to regulate gene expression and cellular network processes. More and more evidence shows thatmiRNAs play an important role in regulating macrophage polarization. Therefore, in this review, miRNAsregulating macrophage polarization to M1 / M2 type and have bidirectional regulation function are listed, and how they regulate macrophage polarization through transcription factors and their potential in thetreatment of inflammation and tumor.
ABSTRACT
MicroRNA (miRNA) is a class of endogenous non-coding single-stranded RNA molecules with a length of about 16 ~ 29 nucleotides. Widely found in eukaryotes, they play important regulatory roles in plant cell proliferation and differentiation, organ formation, metabolism, resistance to salt, temperature, drought, heavy metal stress, etc. Plant miRNA mainly affects plant growth and development by degrading target genes or inhibiting the expression of target genes at the translation level. At present, the research on the production and regulation of miRNA is relatively clear, and the specific roles and regulatory networks of miRNA in plant secondary metabolism and response to abiotic stress have also been identified, which lays the foundation for a full understanding of the molecular regulation of miRNA. In order to better understand the expression and regulation characteristics of miRNA and to interpret the regulatory network of miRNA in plant secondary metabolism and abiotic stress response, we review the molecular mechanisms of plant miRNAs in regulating the biosynthesis of various secondary metabolites(flavonoids, terpenoids, alkaloids) and responding to environmental stress (salt, high temperature, low temperature, drought, heavy metal stress),and summarize the regulatory roles of miRNA in secondary metabolism and abiotic stress, which will provide references for understanding the relationship between environmental stress and plant metabolism, for further studying the regulatory mechanism of miRNA in maintaining plant homeostasis, and for cultivating superior crop varieties.
ABSTRACT
Exosomal microRNAs (miRNAs) are miRNAs that are mediated by exosomes to achieve cell-to-cell communication, and they are widespread in organisms. In recent years, the key role of the multiple biological functions of exosomal miRNAs in the occurrence and development of cardiovascular diseases has been confirmed by a large number of studies, which has become a hot spot in clinical and basic research. Sudden cardiac death caused by cardiovascular disease is one of the important contents in forensic medical identification. This article introduces the research progress of cardiovascular disease prediction, treatment and prognosis on exosomal miRNA. The prospects of the application in forensic medical identification are discussed.
Subject(s)
Humans , Cardiovascular Diseases/genetics , Exosomes/genetics , MicroRNAs/geneticsABSTRACT
Objective:To investigate the neuroprotective effects of Danggui Shaoyaosan （DSS） on APP<sub>swe</sub>/PS1<sub>ΔE9 </sub>transgenic （APP/PS1） mice and its mechanism related to circular RNA （circRNA）. Method:Totally twenty 6-month-old APP/PS1 mice were divided into model group and DSS group， and 10 C57BL/6 wild-type mice were set as the normal control group. The normal group and model group received the same volume of normal saline， and DSS group received drug by gavage administration， all for 8 weeks. The differentially expressed circRNA of APP/PS1 mice before and after DSS intervention was analyzed by circRNA sequencing to construct circRNA-miRNA mRNA interaction network. The results of cricRNA sequencing were then verified by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of phosphoinositide 3-kinase （PI3K）， p-PI3K， protein kinase B1 （Akt1）， p-Akt1， B lymphocytoma-2 （Bcl-2）， and Bcl-2-Associated X protein （Bax） in the hippocampus were detected by immunoblotting （Western blot）. The protein expression of Caspase-3 in the hippocampus was detected by immunohistochemistry and the level of apoptosis in the hippocampus was detected by the TUNEL method. Result:Compared with the model group， there were 90 differentially expressed circRNA after intervention with DSS， of which 46 were up-regulated and 44 down-regulated. Compared with the normal group， the expression levels of circRNA1398 and circRNA1399 in the model group decreased， and the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p increased. Compared with the model group， the expression levels of circRNA1398 and circRNA1399 in the DSS group were up-regulated， while the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p were down-regulated. Compared with the normal group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the model group decreased （<italic>P</italic><0.05，<italic> P</italic><0.01）， and the expression of Bax and Caspase in the model group increased （<italic>P</italic><0.01）. Compared with the model group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the hippocampus of the DSS group increased （<italic>P</italic><0.01）， and the protein expression of Bax and Caspase decreased （<italic>P</italic><0.01）. Compared with the normal group， the apoptosis level in the hippocampus of the model group increased， with an apoptosis rate of （43.76±2.92）%. Compared with the model group， the apoptosis rate of DSS group was （24.64±3.39）%. Conclusion:DSS can activate PI3K/Akt pathway and inhibit apoptosis in hippocampal neurons of APP / PS1 mice， and play a neuroprotective role. The specific mechanism may be related to the regulation of circRNA1398 and circRNA1399 expression and the corresponding miRNA expression.
ABSTRACT
Objective To screen the secretory factor-related, mechanoresponsive microRNAs (miRNA) of osteocytes. Methods Cyclic mechanical tensile strain (ε=2.5,f=0.5 Hz) was applied to osteocytes and osteoblasts cultured in vitro respectively, and the differentially expressed miRNAs only in the osteocytes were screened out by using miRNA chip. Through bioinformatics technology, in these differentially expressed miRNAs, the target genes of secretory factors including insulin-like growth factor-1(IGF-1), nitric oxide synthesase (NOS), fibroblast growth factor 23 (FGF23) and sclerostin (SOST) were further screened out. Then the selected miRNAs were compared with the biochip detected, differentially expressed miRNAs in femur bone of the mice which were trained on treadmill, and four of these miRNAs were randomly selected for quantitative PCR verification. Results For the 77 differentially expressed miRNAs only in the mechanically strained osteocytes in vitro, 22 miRNAs whose target genes were the 4 secreted factors (IGF-1, NOS, FGF23 and SOST), were screened out. Moreover, a total of 11 miRNAs in the 22 miRNAs were differentially expressed in femur bone of the treadmill trained mice with the same trend as those in osteocytes in vitro, and the randomly selected miR-361-3p, miR-3082-5p, miR-6348 and miR-706 were confirmed to be differentially expressed with the same trend in femur bone and osteocytes. Conclusions These mechanoresponsive miRNAs differentially expressed only in osteocytes, such as miR-361-3p, miR-3082-5p, miR-6348 and miR-706, probably influence osteoblastic differentiation or bone metabolism through regulating the secretory factors.
ABSTRACT
A common pathological features of Alzheimer's disease (AD) is the excessive activation of inositol-requiring enzyme-1α (IRE1α) downstream of endoplasmic reticulum stress (ERS) and the abnormal expression of microRNA (miRNA) with a variety of cellular physiological functions. Studies have found that IRE1α and miRNA are not alone in the AD pathologenesis. IRE1α can regulate the expression of miR-200, miR-7, miR-17 and miR-34, and participate in most AD brain diseases such as Aβ deposition, Tau protein hyperphosphorylation and neuronal apoptosis. It is suggested that IRE1α-miRNA signal abnormality is one of the pathological mechanisms of AD. Exercise can prevent and delay AD, but its mechanism is unclear. Studies have found that exercise could interfere with AD by regulating the IRE1αmiRNA signaling pathway. The specific mechanisms of action include: (1) Exercise improves the adaptation of AD brain energy metabolism and alleviates the excessive activation of brain IRE1α signals. (2) Exercise regulates the expression of miRNA in the brain, exerts epigenetic effects, and reduces pathologies such as Aβ and Tau protein aggregation. (3) The IRE1α-miRNA pathway and its downstream protein changes can mediate exercise to resist the development of AD. This article will review the relationship between IRE1α-miRNA and AD pathology and its exercise feedback mechanism, aiming to provide evidence and ideas for AD diagnosis and treatment strategies.
ABSTRACT
Exosome is a kind of vesicular body which can be secreted by most cells and can communicate information between cells through the transfer of specific signal molecules. More and more studies have shown that exosomes are widely involved in the occurrence and development of cardiovascular diseases, such as hypertension, heart failure and myocardial infarction. In recent years, studies have shown that exercise has a great impact on the biological function of body fluids and blood circulation exosomes. Different exercise modes can promote the release of exosomes and affect the expression of miRNA and proteins. At present, studies have found that exercise promotion of exosome release may be related to the laminar shear force induced by blood flow, the increase of Ca
ABSTRACT
G-quadruplex (G4) is a non-canonical nucleic acid secondary structure composed of guanine-rich DNA or RNA sequences. In the past few decades, researchers have focused on the G-rich sequences in gene promoter region, UTR, telomere and other common gene functional regions, to understand the relationship between their structure and function. In recent years, due to the in-depth study of non-coding RNA in diseases, G-rich sequences in non-coding RNA, especially miRNA, have attracted more attention. G-rich sequence has been involved in all physiological processes of miRNA synthesis, from primary miRNA (pri-miRNA), precursor miRNA (pre-miRNA) to mature miRNA: the dynamic balance formed between the G-quadruplex and the RNA stem-loop structure affects the maturation process of primary and precursor miRNA, causing the change of mature miRNA and the complementary pairing between miRNA and mRNA. This review focused on the dynamic changes between G4 and hairpin structure, and expounded the role of G-rich sequence in pri-miRNA, pre-miRNA, mature miRNA and mRNA. The important role of G-quadruplex in the maturation and function of miRNA was also discussed. It was concluded that the changes of external regulatory factors such as ionic conditions (K+, Mg +, K+ + Mg, Li +Mg +, etc) and G-quadruplex ligand molecules (destabilizer TMPyP4, etc) could regulate the balance between G-quadruplex and stem-loop structure, thus modulating the functions of miRNA. This review may help providing ideas and directions for the study of G-quadruplex function and regulation.
ABSTRACT
@#[Abstract] Objective: To investigate the miR-423-5p expression in brain glioma tissues and cell lines, and its promotive effect on temozolomide (TMZ) chemoresistance by targeting PDCD5 (programmed cell death protein 5). Methods: Tumor tissues and matched peritumoral tissues were collected from 20 brain glioma patients who were surgically treated in the Department of Neurosurgery, Affiliated Hospital of Beihua University between January 2017 and December 2018. Glioblastoma cell lines (U251, U87, SHG-44) and human normal glial cell line HMC-3 were also used in the study. The relative expression of miR-423-5p and PDCD5 in brain glioma and peritumoral tissues and cell lines was detected by qPCR. The synthesized miR-423-5p mimics and miR-NC were respectively transfected into U251 and U87 cells; meanwhile, TMZ at different concentrations (50, 100, 150 and 200 μmol/L) were also used to treat the cells. Then, the chemoresistance of cells to TMZ were determined. MTT assay and colony formation assay were used to examine the proliferation of U251 and U87 cells, andWestern blotting was used to detect the expression of c-caspase 3, Bcl-2 and PDCD5 proteins in U251 and U87 cells. The targeting relationship between PDCD5 and miR-423-5p was validated through Dual luciferase reporter gene assay. Results: miR-423-5p was highly expressed in glioma tissues and glioma cell lines (all P<0.01). As compared with the miR-NC group, the proliferation and TMZ-chemoresistance of U251 and U87 cells in miR-423-5p mimics group significantly increased (all P<0.01). Dual luciferase reporter gene assay validated that miR-423-5p could bind with PDCD5 3' UTR to suppress the expression of PDCD5. Conclusion: High expression of miR-423-5p enhances the chemoresistance of glioma cells to TMZ, and miR-423-5p may serve as a potential therapeutic target in the treatment of brain glioma.