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1.
DNA Cell Biol ; 40(6): 740-747, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34015233

RESUMO

MicroRNA is a small noncoding RNA that plays a role in regulating gene expression. miR-1271 is a tumor suppressor microRNA, which is related to the biological changes of many cancers. miR-1271 is considered a biomarker with a potential prognosis and high therapeutic value in tumors. Besides, the expression of miR-1271 is also regulated by many factors. In this study, we summarize the role of miR-1271 in tumors, focusing on the molecular mechanisms of the target genes of miR-1271. Our review will provide a comprehensive understanding of miR-1271 in tumors, as well as ideas for subsequent tumor research related to miR-1271.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , MicroRNAs/fisiologia , Neoplasias/metabolismo , Biomarcadores Tumorais/fisiologia , Humanos , Neoplasias/genética , Transdução de Sinais
2.
Toxicol Lett ; 348: 50-58, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34052307

RESUMO

Antimony is a common environmental contaminant that causes biological toxicity in exposed populations worldwide. Previous studies have revealed that antimony promotes prostate cancer growth by stabilizing the c-Myc protein and mimicking androgen activity. However, the role of lncRNAs in the regulation of antimony-induced carcinogenesis remains unknown, and the precise mechanisms need to be explored. In the present study, we found that chronic exposure to antimony promoted cell growth and lipid metabolic disequilibrium in prostate cancer. Mechanistically, we identified a long noncoding RNA molecule, PCA3, that was substantially upregulated in LNCaP cells in response to long-term antimony exposure. Functional studies indicated that abnormal PCA3 expression modulated antimony-induced proliferation and cellular triglyceride and cholesterol levels. In addition, PCA3 levels were found to be inversely correlated with MIR-132-3 P levels by acting as a decoy for MIR-132-3P. Besides, SREBP1 directly interacted with MIR-132-3 P to increase cell growth and disrupt lipid metabolism by targeting its 3'UTR regions. Taken together, our results revealed that lncRNA PCA3 promotes antimony-induced lipid metabolic disorder in prostate cancer by targeting MIR-132-3 P/SREBP1 signaling.


Assuntos
Antígenos de Neoplasias/fisiologia , Antimônio/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , MicroRNAs/fisiologia , Neoplasias da Próstata/metabolismo , RNA Longo não Codificante/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/fisiologia , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/fisiologia
3.
Toxicol Lett ; 348: 40-49, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34052308

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have an important role in the development and progression of human tumors, including lung cancer. Yet, their role in lung cancer induced by benzo(a)pyrene (B[a]P) remains unclear. In this study, circRNA chips and qRT-PCR were used to examine downregulated circRNAs in malignantly transformed 16HBE cells (16HBE-T) induced by B[a]P. Five down-regulated circRNAs were found, among which hsa_circ_0004552 (circ_CARM1) had the most significant downregulation. Consequently, the role of circ_CARM1 on 16HBE-T cells biological behavior was further examined using several in vitro experiments. MATERIALS AND METHODS: Detecting RNA expression via qRT-PCR. Fluorescence in situ hybridization (FISH) was used to identify the localization of circ_CARM1 in 16HBE-T. The effect of circ_CARM1 on cell behavior (cell migration, proliferation, and apoptosis) was explored by transfecting cells with a vector carrying an overexpression and then using wound healing, transwell migration assay, and flow cytometry. Also, the regulation mechanism for circ_CARM1, miR-1288-3p, and CTNNBIP1 was studied by Dual-Luciferase® Reporter (DLR™) Assay System and western blotting. RESULTS: Reduced expression of circ_CARM1 is observed in 16HBE-T. The overexpression of circ_CARM1 further inhibited the migration of 16HBE-T cells but did not affect cell proliferation and apoptosis. Furthermore, bioinformatic analysis and Dual-Luciferase® Reporter (DLR™) Assay System showed that the competitive binding of circ_CARM1 and miR-1288-3p enhanced the expression of CTNNBIP1, thereby inhibiting the migration of 16HBE-T cells. CONCLUSION: Downregulation of circ_CARM1 can stimulate the expression of miR-1288-3p, thereby reducing the expression of CTNNBIP1, spurring cell migration.


Assuntos
7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Pulmonares/patologia , RNA Circular/fisiologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Transformação Celular Neoplásica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/induzido quimicamente , MicroRNAs/fisiologia
4.
Food Funct ; 12(8): 3381-3392, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900350

RESUMO

The effect of non-cytotoxic doses of epigallocatechin-3-gallate (EGCG) on the metastatic capability of human hepatocellular carcinoma (HCC) cells was investigated in vitro and in vivo. miR483-3p, a microRNA whose expression correlates inversely with survival and positively with disease progression in HCC patients, was found to promote HCC cell migration and invasion in vitro as well as lung metastasis in nude mice established by the tail-vein injection of HCC cells. The induction of reactive oxygen species (ROS) and downregulation of antioxidant defense factors Nrf2 and SOD2 appeared to be an important underlying mechanism and treatment with a non-cytotoxic dose of EGCG effectively reversed the miR483-3p-induced enhancement of HCC cell migration and invasion in vitro. Moreover, administration through drinking water at doses (0.1% and 0.5% EGCG solution, respectively) equivalent to the intake of regular to heavy tea drinkers could also significantly inhibit lung metastasis of HCC cells based on the estimation from the USDA Database for the Flavonoid Content of Selected Foods and FDA guidelines for the conversion of animal dose to human equivalent dose. EGCG also significantly counteracted the miR483-3p-induced alteration in the expression of epithelial-mesenchymal transition (EMT) markers, E-cadherin and vimentin, and downregulated the endogenous expression of miR483-3p in HCC cells through an epigenetic mechanism that led to the hypermethylation of the miR483-3p promoter region. The data from our study illustrate that miR483-3p promotes HCC metastasis likely through the induction of oxidative stress and uncover a novel role of EGCG for protection against miR483-3p-mediated HCC metastasis via the epigenetic modulation of miR483-3p expression. These findings therefore provide further evidence supporting that regular tea consumption may contribute to protection against miR-483-3p-induced ROS and the associated HCC progression.


Assuntos
Carcinoma Hepatocelular/patologia , Catequina/análogos & derivados , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Metástase Neoplásica/genética , Animais , Catequina/administração & dosagem , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/fisiologia , Metástase Neoplásica/prevenção & controle , Espécies Reativas de Oxigênio/análise , Soluções , Chá , Transdução Genética
5.
Int J Mol Sci ; 22(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805523

RESUMO

The intestinal epithelium serves as a dynamic barrier to protect the host tissue from exposure to a myriad of inflammatory stimuli in the luminal environment. Intestinal epithelial cells (IECs) encompass differentiated and specialized cell types that are equipped with regulatory genes, which allow for sensing of the luminal environment. Potential inflammatory cues can instruct IECs to undergo a diverse set of phenotypic alterations. Aging is a primary risk factor for a variety of diseases; it is now well-documented that aging itself reduces the barrier function and turnover of the intestinal epithelium, resulting in pathogen translocation and immune priming with increased systemic inflammation. In this study, we aimed to provide an effective epigenetic and regulatory outlook that examines age-associated alterations in the intestines through the profiling of microRNAs (miRNAs) on isolated mouse IECs. Our microarray analysis revealed that with aging, there is dysregulation of distinct clusters of miRNAs that was present to a greater degree in small IECs (22 miRNAs) compared to large IECs (three miRNAs). Further, miRNA-mRNA interaction network and pathway analyses indicated that aging differentially regulates key pathways between small IECs (e.g., toll-like receptor-related cascades) and large IECs (e.g., cell cycle, Notch signaling and small ubiquitin-related modifier pathway). Taken together, current findings suggest novel gene regulation pathways by epithelial miRNAs in aging within the gastrointestinal tissues.


Assuntos
Envelhecimento/fisiologia , Células Epiteliais/fisiologia , Mucosa Intestinal/citologia , MicroRNAs/fisiologia , Animais , Simulação por Computador , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Intestino Grosso/citologia , Intestino Delgado/citologia , Camundongos Endogâmicos C57BL , RNA Mensageiro
6.
Mol Genet Genomics ; 296(4): 765-781, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33904988

RESUMO

The genome could be considered as raw data expressed in proteins and various types of noncoding RNAs (ncRNAs). However, a large portion of the genome is dedicated to ncRNAs, which in turn represent a considerable amount of the transcriptome. ncRNAs are modulated on levels of type and amount whenever any physiological process occurs or as a response to external modulators. ncRNAs, typically forming complexes with other partners, are key molecules that influence diverse cellular processes. Based on the knowledge of mammalian biology, ncRNAs are known to regulate and control diverse trafficking pathways and cellular activities. Long noncoding RNAs (lncRNAs) notably have diverse and more regulatory roles than microRNAs. Expanding these studies on fish has derived the same conclusion with relevance to other species, including invertebrates, explored the potentials to harness such types of RNA to further understand the biology of such organisms, and opened gates for applying recent technologies, such as RNA interference and delivering micromolecules as microRNAs to living cells and possibly to target organs. These technologies should improve aquaculture productivity and fish health, as well as help understand fish biology.


Assuntos
Peixes , Imunidade/genética , RNA não Traduzido/fisiologia , Animais , Peixes/genética , Peixes/imunologia , MicroRNAs/fisiologia , Interferência de RNA/fisiologia , RNA Longo não Codificante/fisiologia , Transcriptoma/fisiologia
7.
Life Sci ; 277: 119484, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33862119

RESUMO

As a type of non-coding RNA, microRNAs are considered to be a new regulator in viral infections. Influenza A (H1N1) virus infection is a serious threat to human health. There is growing evidence supporting that microRNAs play important roles in various cellular infection stages and host antiviral response during H1N1 infection. Some microRNAs defend against H1N1 invasion, while others may promote viral replication. MicroRNAs are implicated in the host-viral interactions and serve versatile functions in it. In this review, we focus on the innate immune response and virus replication regulated by microRNAs during H1N1 infection. MicroRNAs can influence H1N1 virus replication by directly binding to viral compositions and through host cellular pathways. Moreover, microRNAs are involved in multiple antiviral response, including production of interferons (IFNs), retinoic acid-inducible gene I (RIG-I) signaling pathway, immune cells development and secretion, activation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB). Furthermore, these regulatory effects of microRNAs suggest its potential clinical significance. In addition, another non-coding RNA, lncRNA, are also mentioned in the review, which can regulate innate immune response and influence virus replication during H1N1 infection as well.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/genética , MicroRNAs/genética , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Imunidade Inata/imunologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/metabolismo , Interferons/metabolismo , MicroRNAs/fisiologia , Transdução de Sinais/genética , Replicação Viral/genética
8.
Diabetes Res Clin Pract ; 176: 108837, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33901624

RESUMO

BACKGROUND: CircRNAs are reported to be aberrantly expressed and perform biological functions in diverse processes. This study aimed to investigate the potential involvement of hsa_circ_0054633 in high glucose (HG)­induced diabetic model and its potential mechanism. METHODS: The expression of hsa_circ_0054633, miR-409-3p and caspase-8 was detected by real-time PCR and western blotting. Cell viability, apoptosis and the protein levels of apoptosis-related factors were revealed by CCK-8 colorimetry, flow cytometry and western blotting, respectively. Insulin secretion was determined by enzyme-linked immunosorbent assay (ELISA) and the measurement of insulin-related transcription factors. The target association between miR-409-3p and hsa_circ_0054633 or caspase-8 was confirmed by dual-luciferase reporter assays and biotin-based pulldown assay. RESULTS: Hsa_circ_0054633 was highly expressed and the expression of miR-409-3p was downregulated in serum of DM patients and HG-treated human pancreatic ß cell line NES2Y. Further investigation indicated that hsa_circ_0054633 suppression promoted cell proliferation, inhibited apoptosis and facilitated insulin secretion in HG-treated NES2Y cells. Mechanical analysis revealed that hsa_circ_0054633 regulated caspase-8 expression via sponging miR-409-3p. Rescue experiments demonstrated that miR-409-3p knockdown or caspase-8 overexpression reversed the effects of hsa_circ_0054633 in HG-stimulated NES2Y cells. CONCLUSION: Inhibition of hsa_circ_0054633 protected against HG-induced NES2Y cell apoptosis and impairment of insulin secretion by regulating miR-409-3p/caspase-8 axis.


Assuntos
Apoptose/genética , Secreção de Insulina/genética , Células Secretoras de Insulina/fisiologia , RNA Circular/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Caspase 8/genética , Caspase 8/fisiologia , Proliferação de Células/genética , Células Cultivadas , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Células Secretoras de Insulina/metabolismo , Masculino , MicroRNAs/genética , MicroRNAs/fisiologia , Pessoa de Meia-Idade , Transdução de Sinais/genética , Adulto Jovem
9.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800752

RESUMO

The members of the B7 family, as immune checkpoint molecules, can substantially regulate immune responses. Since microRNAs (miRs) can regulate gene expression post-transcriptionally, we conducted a scoping review to summarize and discuss the regulatory cross-talk between miRs and new B7 family immune checkpoint molecules, i.e., B7-H3, B7-H4, B7-H5, butyrophilin like 2 (BTNL2), B7-H6, B7-H7, and immunoglobulin like domain containing receptor 2 (ILDR2). The current study was performed using a six-stage methodology structure and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Embase, Scopus, Cochrane, ProQuest, and Google Scholar were systematically searched to obtain the relevant records to 5 November 2020. Two authors independently reviewed the obtained records and extracted the desired data. After quantitative and qualitative analyses, we used bioinformatics approaches to extend our knowledge about the regulatory cross-talk between miRs and the abovementioned B7 family members. Twenty-seven articles were identified that fulfilled the inclusion criteria. Studies with different designs reported gene-miR regulatory axes in various cancer and non-cancer diseases. The regulatory cross-talk between the aforementioned B7 family molecules and miRs might provide valuable insights into the pathogenesis of various human diseases.


Assuntos
Antígenos B7/fisiologia , Proteínas de Checkpoint Imunológico/fisiologia , MicroRNAs/fisiologia , Antígenos B7/genética , Antígenos B7/imunologia , Coagulação Sanguínea , Quimiocinas/fisiologia , Ativação do Complemento , Biologia Computacional/métodos , Doença/genética , Redes Reguladoras de Genes , Humanos , Proteínas de Checkpoint Imunológico/genética , Proteínas de Checkpoint Imunológico/imunologia , MicroRNAs/genética , Transdução de Sinais
10.
Metabolism ; 119: 154768, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33775647

RESUMO

BACKGROUND: Reducing serum low-density lipoprotein cholesterol (LDL-C) in hyperlipemia is recognized as an effective strategy to minimize the risk of atherosclerotic cardiovascular disease (ASCVD). MiR-337-3p has already been discovered to play regulatory roles in tumor proliferation and metastasis, adipocyte browning and ischemic brain injury, etc. However, the association between miR-337-3p and LDL-C is unknown. METHODS: Gene Expression Omnibus (GEO) dataset and two hyperlipidemic murine models were used to analyze the potential relationship between miR-337-3p and LDL-C. AAV-mediated liver-directed miRNA overexpression in high fat diet (HFD)-fed mouse model was used to examine the effect of miR-337-3p on LDL-C and WB/RT-PCR/ELISA/luciferase assays were used to investigate the underlying mechanism. RESULTS: The expressions of miR-337-3p were obviously lower in multiple hyperlipidemic mouse models and had a negative correlation with serum LDL-C levels. After confirming the effect of miR-337-3p on the improvement of serum LDL-C in vivo, we discovered PCSK9 might be a possible target of miR-337-3p, which was further proved by in vitro experiments. MiR-337-3p could directly interact with both the PCSK9 3'UTR and promoter to inhibit PCSK9 translation and transcription. Furthermore, the result from DiI-LDL uptake assay under the knockdown of PCSK9 demonstrated that miR-337-3p promoting the absorption of LDL-C in HepG2 cells was dependent on PCSK9, and the result from LDLR-/- mouse model indicated that miR-337-3p regulating LDL-C was dependent on PCSK9/LDLR pathway. CONCLUSION: We discovered a new function of miR-337-3p in regulating PCSK9 expression and LDL-C absorption, suggesting miR-337-3p might be a new therapeutic target for the development of antihyperlipidemic drug.


Assuntos
LDL-Colesterol/sangue , Hiperlipidemias/genética , MicroRNAs/fisiologia , Pró-Proteína Convertase 9/genética , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Regulação da Expressão Gênica , Células HEK293 , Células Hep G2 , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Hiperlipidemias/patologia , Metabolismo dos Lipídeos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética
11.
BMC Plant Biol ; 21(1): 132, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750309

RESUMO

BACKGROUND: Tartary buckwheat seed development is an extremely complex process involving many gene regulatory pathways. MicroRNAs (miRNAs) have been identified as the important negative regulators of gene expression and performed crucial regulatory roles in various plant biological processes. However, whether miRNAs participate in Tartary buckwheat seed development remains unexplored. RESULTS: In this study, we first identified 26 miRNA biosynthesis genes in the Tartary buckwheat genome and described their phylogeny and expression profiling. Then we performed small RNA (sRNA) sequencing for Tartary buckwheat seeds at three developmental stages to identify the miRNAs associated with seed development. In total, 230 miRNAs, including 101 conserved and 129 novel miRNAs, were first identified in Tartary buckwheat, and 3268 target genes were successfully predicted. Among these miRNAs, 76 exhibited differential expression during seed development, and 1534 target genes which correspond to 74 differentially expressed miRNAs (DEMs) were identified. Based on integrated analysis of DEMs and their targets expression, 65 miRNA-mRNA interaction pairs (25 DEMs corresponding to 65 target genes) were identified that exhibited significantly opposite expression during Tartary buckwheat seed development, and 6 of the miRNA-mRNA pairs were further verified by quantitative real-time polymerase chain reaction (qRT-PCR) and ligase-mediated rapid amplification of 5' cDNA ends (5'-RLM-RACE). Functional annotation of the 65 target mRNAs showed that 56 miRNA-mRNA interaction pairs major involved in cell differentiation and proliferation, cell elongation, hormones response, organogenesis, embryo and endosperm development, seed size, mineral elements transport, and flavonoid biosynthesis, which indicated that they are the key miRNA-mRNA pairs for Tartary buckwheat seed development. CONCLUSIONS: Our findings provided insights for the first time into miRNA-mediated regulatory pathways in Tartary buckwheat seed development and suggested that miRNAs play important role in Tartary buckwheat seed development. These findings will be help to study the roles and regulatory mechanism of miRNAs in Tartary buckwheat seed development.


Assuntos
Fagopyrum/crescimento & desenvolvimento , Fagopyrum/genética , MicroRNAs/fisiologia , RNA Mensageiro/fisiologia , RNA de Plantas/fisiologia , Sementes/crescimento & desenvolvimento , Evolução Molecular , Perfilação da Expressão Gênica , Reação em Cadeia da Ligase , MicroRNAs/genética , Filogenia , Desenvolvimento Vegetal/genética , RNA de Plantas/genética , Reação em Cadeia da Polimerase em Tempo Real , Sementes/genética
12.
BMC Plant Biol ; 21(1): 155, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771101

RESUMO

BACKGROUND: Anastomosis group 1 IA (AG1-IA) of Rhizoctonia solani is the major agent of banded leaf and sheath blight (BLSB) disease that causes severe yield loss in many worldwide crops. MicroRNAs (miRNAs) are ~ 22 nt non-coding RNAs that negatively regulate gene expression levels by mRNA degradation or translation inhibition. A better understanding of miRNA function during AG1-IA infection can expedite to elucidate the molecular mechanisms of fungi-host interactions. RESULTS: In this study, we sequenced three small RNA libraries obtained from the mycelium of AG1-IA isolate, non-infected maize sheath and mixed maize sheath 3 days after inoculation. In total, 137 conserved and 34 novel microRNA-like small RNAs (milRNAs) were identified from the pathogen. Among these, one novel and 17 conserved milRNAs were identified as potential virulence-associated (VA) milRNAs. Subsequently, the prediction of target genes for these milRNAs was performed in both AG1-IA and maize, while functional annotation of these targets suggested a link to pathogenesis-related biological processes. Further, expression patterns of these virulence-associated milRNAs demonstrated that theyparticipate in the virulence of AG1-IA. Finally, regulation of one maize targeting gene, GRMZM2G412674 for Rhi-milRNA-9829-5p, was validated by dual-luciferase assay and identified to play a positive role in BLSB resistance in two maize mutants. These results suggest the global differentially expressed milRNAs of R. solani AG1-IA that participate in the regulation of target genes in both AG1-IA and maize to reinforce its pathogenicity. CONCLUSIONS: Our data have provided a comprehensive overview of the VA-milRNAs of R. solani and identified that they are probably the virulence factors by directly interfered in host targeting genes. These results offer new insights on the molecular mechanisms of R.solani-maize interactions during the process of infection.


Assuntos
MicroRNAs/fisiologia , Doenças das Plantas/microbiologia , Rhizoctonia/patogenicidade , Zea mays/microbiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , Doenças das Plantas/genética , RNA Bacteriano/fisiologia , Rhizoctonia/genética , Virulência/genética , Zea mays/genética
13.
BMC Cancer ; 21(1): 255, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750326

RESUMO

BACKGROUND: Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis. METHODS: RNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm. RESULTS: A prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types. CONCLUSIONS: MIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma.


Assuntos
Neoplasias Colorretais/genética , MicroRNAs/fisiologia , Proteínas do Tecido Nervoso/fisiologia , RNA Longo não Codificante/fisiologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Imuno-Histoquímica , MicroRNAs/análise , Prognóstico , Mapas de Interação de Proteínas , RNA Longo não Codificante/análise , RNA Mensageiro/análise , RNA Mensageiro/fisiologia , Microambiente Tumoral
14.
Life Sci ; 275: 119323, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33744323

RESUMO

MiR-375, a primitively described beta cell-specific miRNA, is confirmed to function as multi-functional regulator in diverse typical cellular pathways according to the follow-up researches. Based on the existing studies, miR-375 can regulate many functional genes and ectopic expressions of miR-375 are usually associated with pathological changes, and its expression regulation mechanism is mainly related to promoter methylation or circRNA. In this review, the regulatory functions of miR-375 in immunity, such as its relevance with macrophages, T helper cells and autoimmune diseases were briefly discussed. Also, the functions of miR-375 involved in inflammation, development and virus replication were reviewed. Finally, the mechanisms and application prospects of miR-375 in cancers were analyzed. Studies show that the application of miR-375 as therapeutic target and biomarker has a broad developing space in future. We hope this paper can provide reference for its further study.


Assuntos
MicroRNAs/fisiologia , Animais , Humanos , Imunidade , Inflamação/metabolismo , Camundongos , MicroRNAs/metabolismo , Neoplasias/metabolismo , Ratos
15.
J Orthop Surg Res ; 16(1): 105, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530998

RESUMO

BACKGROUND: Synovial fibroblasts (SFs) with the abnormal expressions of miRNAs are the key regulator in rheumatoid arthritis (RA). Low-expressed miR-140-3p was found in RA tissues. Therefore, we attempted to investigate the effect of miR-140-3p on SFs of RA. METHODS: RA and normal synovial fibrous tissue were gathered. The targets of miR-140-3p were found by bioinformatics and luciferase analysis. Correlation between the expressions of miR-140-3p with sirtuin 3 (SIRT3) was analyzed by Pearson correlation analysis. After transfection, cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry. The expressions of miR-140-3p, SIRT3, Ki67, Bcl-2, Bax, and cleaved Caspase-3 were detected by RT-qPCR or western blot. RESULTS: Low expression of miR-140-3p and high expression of SIRT3 were found in RA synovial fibrous tissues. SIRT3 was a target of miR-140-3p. SIRT3 expression was negatively correlated to the expression of miR-140-3p. MiR-140-3p mimic inhibited the MH7A cell viability and the expressions of SIRT3, Ki67, and Bcl-2 and promoted the cell apoptosis and the expressions of Bax and cleaved Caspase-3; miR-140-3p inhibitor showed an opposite effect to miR-140-3p mimic on MH7A cells. SIRT3 overexpression not only promoted the cell viability and inhibited cell apoptosis of MH7A cells but also reversed the effect of miR-140-3p mimic had on MH7A cells. CONCLUSIONS: The results in this study revealed that miR-140-3p could inhibit cell viability and promote apoptosis of SFs in RA through targeting SIRT3.


Assuntos
Apoptose/genética , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Sobrevivência Celular/genética , Fibroblastos/patologia , MicroRNAs/genética , MicroRNAs/fisiologia , Sirtuína 3/genética , Sirtuína 3/metabolismo , Membrana Sinovial/citologia , Células Cultivadas , Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , MicroRNAs/metabolismo
16.
Gynecol Obstet Invest ; 86(1-2): 108-116, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33596588

RESUMO

BACKGROUND: MicroRNAs are endogenous small noncoding RNAs, which play a critical role in regulating various biological and pathologic processes. Furthermore, miR-301a has been detected to be overly expressed in tumorigenic progression of ovarian cancer. However, the effects of miR-301a on ovarian cancer are still unclear. OBJECTIVE: The objective of this study is to investigate the molecular mechanisms of miR-301a in epithelial ovarian cancer cells. METHODS: The miR-301a expression in ovarian cancer cells was detected. Then, cell proliferation, cell cycle, and apoptosis of the miR-301a-mimic-transfected ovarian cancer cells were determined, as well as the effects of the miR-301a mimic on the PTEN/phosphoinositide 3-kinase (PI3K) signaling pathway were explored. RESULTS: We found that the miR-301a expression levels were markedly upregulated in ovarian cancer tissues and cells, and upregulation of miR-301a-promoted cell viability and proliferation. Our results also showed that the miR-301a-mimic accelerated cell cycle progression of ovarian cancer cells by targeting the CDK4/Cyclin-D1 pathway but not the CDK2/Cyclin-E pathway. Moreover, transfection of the miR-301a mimic into ovarian cancer cells could decrease the PTEN expression while increasing the PI3K and Akt phosphorylation, as compared with the miR-301a inhibitor group and the negative control group. CONCLUSION: Therefore, miR-301a should be an oncogene in ovarian cancer, and overexpression of miR-301a promoted proliferation of ovarian cancer cells by modulating the PTEN/PI3K/Akt signaling pathway.


Assuntos
Apoptose/fisiologia , Proliferação de Células/fisiologia , MicroRNAs/fisiologia , Neoplasias Ovarianas/patologia , Transdução de Sinais/fisiologia , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transfecção
17.
Life Sci ; 275: 119273, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33631172

RESUMO

AIMS: Postmenopausal osteoporosis (PMOP) is a growing health problem affecting many postmenopausal women. This study intended to identify the role of dexmedetomidine (Dex) in osteoporosis (OP). MAIN METHODS: Microarray analysis was performed for the gene expression profiles of PMOP patients and postmenopausal healthy volunteers, and the most differentially expressed microRNA (miR)-361-5p was verified in clinic, and its diagnostic value in PMOP patients was analyzed. After establishment of OP model by ovariectomy, Dex treatment and overexpression of miR-361-5p or vascular endothelial growth factor A (VEGFA) were performed in OP rats or isolated bone marrow mesenchymal stem cells (BMSCs). Bone mineral density (BMD) related indexes and levels of osteogenesis-angiogenesis related genes were measured. The apoptosis and osteogenic differentiation of BMSCs were detected. After human umbilical vein endothelial cells (HUVECs) and BMSCs were cocultured, the angiogenesis of BMSCs was detected by Matrigel-based angiogenesis experiment. KEY FINDINGS: miR-361-5p was highly expressed in PMOP patients and OP rats, with good diagnostic effect on PMOP. After Dex treatment, the expressions of miR-361-5p, VEGFA, BMD related indexes were increased in OP rats. In BMSCs, level of osteogenesis-angiogenesis related genes were increased after adding Dex, and the apoptosis was decreased after coculture of HUVECs and BMSCs. miR-361-5p could target VEGFA. After miR-361-5p overexpression + Dex treatment, the indexes related to osteogenesis and angiogenesis in OP rats and BMSCs were decreased, which were reversed after further overexpressing VEGFA. SIGNIFICANCE: Dex can enhance VEGFA by inhibiting miR-361-5p, and then promote osteogenesis-angiogenesis, thus providing potential targets for PMOP treatment.


Assuntos
Dexmedetomidina/farmacologia , MicroRNAs/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Animais , Densidade Óssea , Dexmedetomidina/uso terapêutico , Feminino , Citometria de Fluxo , Humanos , MicroRNAs/fisiologia , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Osteoporose Pós-Menopausa/fisiopatologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Fator A de Crescimento do Endotélio Vascular/fisiologia
18.
Methods Mol Biol ; 2235: 139-153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33576975

RESUMO

MicroRNAs (miRNAs) are expressed in all cell types, including pericytes, and play essential roles in vascular development, homeostasis, and disease. Manipulation of pericytes with miRNA mimics and inhibitors represents an essential tool to study the role of pericytes in vascular development and regeneration and to better understand the therapeutic potential of miRNA manipulation in pericytes. Here we describe methods for manipulating pericyte function by using miRNA mimics and inhibitors. We also describe methods to assess pericyte function (proliferation and migration) after manipulation with miRNAs and explain how miRNA gene targets can be identified and validated in pericytes after manipulation with miRNA.


Assuntos
Clonagem Molecular/métodos , MicroRNAs/genética , Pericitos/metabolismo , Animais , Regulação da Expressão Gênica/genética , Humanos , MicroRNAs/fisiologia , Pericitos/fisiologia , Transfecção/métodos , Transformação Genética/genética
19.
BMC Urol ; 21(1): 5, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407350

RESUMO

BACKGROUND: Emerging evidence has noted the important participation of microRNAs (miRNAs) in several human diseases including cancer. This research was launched to probe the function of miR-381 in bladder cancer (BCa) progression. METHODS: Twenty-eight patients with primary BCa were included in this study. Cancer tissues and the adjacent normal tissues were obtained. Aberrantly expressed miRNAs in BCa tissues were analyzed using miRNA microarrays. miR-381 expression in the bladder and paired tumor tissues, and in BCa and normal cell lines was determined. The target relationship between miR-381 and BMI1 was predicted online and validated through a luciferase assay. Gain-of-functions of miR-381 and BMI1 were performed to identify their functions on BCa cell behaviors as well as tumor growth in vivo. The involvement of the Rho/ROCK signaling was identified. RESULTS: miR-381 was poor regulated in BCa tissues and cells (all p < 0.05). A higher miR-381 level indicated a better prognosis of patients with BCa. Artificial up-regulation of miR-381 inhibited proliferation, invasion, migration, resistance to apoptosis, and tumor formation ability of BCa T24 and RT4 cells (all p < 0.05). miR-381 was found to directly bind to BMI1 and was negatively correlated with BMI1 expression. Overexpression of BMI1 partially blocked the tumor suppressing roles of miR-381 in cell malignancy and tumor growth (all p < 0.05). In addition, miR-381 led to decreased RhoA phosphorylation and ROCK2 activation, which were also reversed by BMI1 (all p < 0.05). Artificial inhibition of the Rho/ROCK signaling blocked the functions of BMI1 in cell growth and metastasis (all p < 0.05). CONCLUSION: The study evidenced that miR-381 may act as a beneficiary biomarker in BCa patients. Up-regulation of miR-381 suppresses BCa development both in vivo and in vitro through BMI1 down-regulation and the Rho/ROCK inactivation.


Assuntos
MicroRNAs/fisiologia , Complexo Repressor Polycomb 1/fisiologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Quinases Associadas a rho/fisiologia , Proteína rhoA de Ligação ao GTP/fisiologia , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Transdução de Sinais
20.
J Orthop Surg Res ; 16(1): 16, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413477

RESUMO

BACKGROUND: MicroRNA (miRNA) plays a vital role in the intervertebral disc (IVD) degeneration. The expression level of miR-573 was downregulated whereas Bax was upregulated notably in human degenerative nucleus pulposus cells. In this study, we aimed to investigate the role of miR-573 in human degenerative nucleus pulposus (NP) cells following hyperbaric oxygen (HBO) treatment. METHODS: NP cells were separated from human degenerated IVD tissues. The control cells were maintained in 5% CO2/95% air and the hyperoxic cells were exposed to 100% O2 at 2.5 atmospheres absolute. MiRNA expression profiling was performed via microarray and confirmed by real-time PCR, and miRNA target genes were identified using bioinformatics and luciferase reporter assays. The mRNA and protein levels of Bax were measured. The proliferation of NPCs was detected using MTT assay. The protein expression levels of Bax, cleaved caspase 9, cleaved caspase 3, pro-caspase 9, and pro-caspase 3 were examined. RESULTS: Bioinformatics analysis indicated that the 3' untranslated region (UTR) of the Bax mRNA contained the "seed-matched-sequence" for hsa-miR-573, which was validated via reporter assays. MiR-573 was induced by HBO and simultaneous suppression of Bax was observed in NP cells. Knockdown of miR-573 resulted in upregulation of Bax expression in HBO-treated cells. In addition, overexpression of miR-573 by HBO increased cell proliferation and coupled with inhibition of cell apoptosis. The cleavage of pro-caspase 9 and pro-caspase 3 was suppressed while the levels of cleaved caspase 9 and caspase 3 were decreased in HBO-treated cells. Transfection with anti-miR-573 partly suppressed the effects of HBO. CONCLUSION: Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative NP cells following HBO treatment.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Oxigenação Hiperbárica , MicroRNAs/fisiologia , Núcleo Pulposo/citologia , Proteína X Associada a bcl-2/metabolismo , Idoso , Células Cultivadas , Feminino , Expressão Gênica/genética , Humanos , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/metabolismo , Proteína X Associada a bcl-2/genética
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