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Cardiovascular disease (CVD) is one of the most threatening diseases to human health and life, and the number of patients is increasing year by year. Thus, it is of great significance to study the pathogenesis, prevention and treatment of CVDs. The occurrence and development of CVDs involve dynamic, complex and delicate intracellular processes and the pathogenesis is not entirely clear. In contrast to genetic mutations, most of the protein post-translational modifications (PTMs) are reversible, and can affect the activity, stability, subcellular localization, protein-protein interaction etc., of the substrate targets, emerging as key mediators of a number of CVD progression. Under pathological conditions, the PTMs undergo aberrant balances which cause changes of the substrate target proteins in expression level, localization and capacity to activate downstream signaling pathways. Therefore, new approaches can be created aiming to correct the abnormal PTM alterations in treating CVDs. This review summarizes some of the more recent advances in PTMs, focusing on SUMOylation, neddylation, succinylation, and prenylation, and the effect of these modifications on cardiovascular function and progression, which may provide potential targets for future therapeutics.
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Doenças Cardiovasculares/metabolismo , Prenilação , Processamento de Proteína Pós-Traducional , Ácido Succínico/metabolismo , Sumoilação , Ubiquitinação , Animais , HumanosRESUMO
Gastric cancer (GC) is one of the most common malignant tumours in the world and has high morbidity and mortality. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently linked circular structures. In recent years, plentiful circRNAs have been discovered that participate in many biological processes, including the initiation and development of tumours. Increasing evidences suggest important biological functions of circRNAs, implying that circRNAs may serve as vital new biomarkers and targets for disease diagnosis and prognosis. Among these, circRNAs are tend to aberrantly expressed and are regarded as potential biomarkers in the carcinogenesis and progression of GC. This review systematically summarised the biogenesis, biological properties and functions of circRNAs, with a focus on their relationship with GC, as well as their probable clinical implications on GC. As our cognition of the relation between circRNAs and GC deepens, more molecular mechanisms of GC progression will be discovered, and new therapeutic strategies will be used for the prevention and treatment of GC.
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Biomarcadores Tumorais , Estudos de Associação Genética , Predisposição Genética para Doença , RNA Circular , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Transcrição Gênica , Animais , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs , Prognóstico , Splicing de RNA , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidadeRESUMO
Accumulation of reactive oxygen species is a common phenomenon in cardiac stress conditions, for instance, coronary artery disease, aging-related cardiovascular abnormalities, and exposure to cardiac stressors such as hydrogen peroxide (H2O2). Mitochondrial protein 18 (Mtp18) is a novel mitochondrial inner membrane protein, shown to involve in the regulation of mitochondrial dynamics. Although Mtp18 is abundant in cardiac muscles, its role in cardiac apoptosis remains elusive. The present study aimed to detect the role of Mtp18 in H2O2-induced mitochondrial fission and apoptosis in cardiomyocytes. We studied the effect of Mtp18 in cardiomyocytes by modulating its expression with lentiviral construct of Mtp18-shRNA and Mtp18 c-DNA, respectively. We then analyzed mitochondrial morphological dynamics with MitoTracker Red staining; apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) and cell death detection assays; and protein expression with immunoblotting. Here, we observed that Mtp18 could regulate oxidative stress- mediated mitochondrial fission and apoptosis in cardiac myocytes. Mechanistically, we found that Mtp8 induced mitochondrial fission and apoptosis by enhancing dynamin-related protein 1 (Drp1) accumulation. Conversely, knockdown of Mtp18 interfered with Drp1-associated mitochondrial fission and subsequent activation of apoptosis in both HL-1 cells and primary cardiomyocytes. However, overexpression of Mtp18 alone was not sufficient to execute apoptosis when Drp1 was minimally expressed, suggesting that Mtp18 and Drp1 are interdependent in apoptotic cascade. Together, these data highlight the role of Mtp18 in cardiac apoptosis and provide a novel therapeutic insight to minimize cardiomyocyte loss via targetting mitochondrial dynamics.
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Apoptose/fisiologia , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/fisiologia , Animais , Peróxido de Hidrogênio/metabolismo , Dinâmica Mitocondrial/fisiologia , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
The pathogenesis of cardiac hypertrophy is tightly associated with mitochondrial dysfunction. Disequilibrium of mitochondrial dynamic is one of the main drivers in the pathological processes during development of various cardiac diseases. However, the effect of mitochondrial dynamics on cardiac hypertrophy remains largely unclear. MicroRNAs (miRNAs) are small noncoding RNAs that can switch off expression of many genes. Mitochondrial anchored protein ligase (MAPL) is a small ubiquitin-like modifier (SUMO) E3 ligase, which is an important contributor in mitochondrial fission process. In this study, we found that hypertrophic agonist phenylephrine (PE) enhanced the expression of MAPL and promoted mitochondrial fission, while it decreased the expression of mitochondrial fusion protein2 (Mfn2) in hypertrophic cardiomyocytes. Silencing expression of MAPL by siRNA attenuated PE-induced depletion of Mfn2 and increase of mitochondrial fission as well as hypertrophic response in cultured primary cardiomyocytes. MiR-485-5p is screened as a candidate inhibitor of MAPL. Overexpression of miR-485-5p blocked mitochondrial fission and hypertrophy induced by PE through inhibiting MAPL expression and increasing the level of Mfn2 in cultured primary cardiomyocytes. In mice model of cardiac hypertrophy induced by PE, the administration of miR-485-5p agomir significantly decreased the PE induced increase in the expression of MAPL and hypertrophic markers (ANP and ß-MHC) along with protection of cardiac structure and function. Together, this study exhibits a novel signaling axis composed of miR-485-5p/MAPL/Mfn2, which regulates mitochondrial machinery and cardiac hypertrophy.
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Cardiomegalia/metabolismo , MicroRNAs/metabolismo , Mitocôndrias Cardíacas/metabolismo , Dinâmica Mitocondrial , Proteínas Mitocondriais/biossíntese , Miócitos Cardíacos/metabolismo , Ubiquitina-Proteína Ligases/biossíntese , Animais , Cardiomegalia/patologia , GTP Fosfo-Hidrolases , Regulação Enzimológica da Expressão Gênica , Proteínas de Membrana/metabolismo , Mitocôndrias Cardíacas/patologia , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Octamer-binding transcription factor 4 (Oct4) is a member of POU (Pit-Oct-Unc) transcription factor family Class V that plays a crucial role in maintaining the pluripotency and self-renewal of stem cells. Though it has been deeply investigated in mammals, its lower vertebrate homologue, especially in the marine fish, is poorly studied. In this study, we isolated the full-length sequence of Paralichthys olivaceus pou5f3 (Popou5f3), and we found that it is homologous to mammalian Oct4. We identified two transcript variants with different lengths of 3'-untranslated regions (UTRs) generated by alternative polyadenylation (APA). Quantitative real-time RT-PCR (qRT-PCR), in situ hybridization (ISH) and immunohistochemistry (IHC) were implemented to characterize the spatial and temporal expression pattern of Popou5f3 during early development and in adult tissues. Our results show that Popou5f3 is maternally inherited, abundantly expressed at the blastula and early gastrula stages, then greatly diminishes at the end of gastrulation. It is hardly detectable from the heart-beating stage onward. We found that Popou5f3 expression is restricted to the adult gonads, and continuously expresses during oogenesis while its dynamics are downregulated during spermatogenesis. Additionally, numerous cis-regulatory elements (CRE) on both sides of the flanking regions show potential roles in regulating the expression of Popou5f3. Taken together, these findings could further our understanding of the functions and evolution of pou5f3 in lower vertebrates, and also provides fundamental information for stem cell tracing and genetic manipulation in Paralichthys olivaceus.
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Sequência Conservada/genética , Desenvolvimento Embrionário/genética , Evolução Molecular , Linguado/embriologia , Linguado/genética , Genômica , Gônadas/embriologia , Fator 3 de Transcrição de Octâmero/genética , Região 5'-Flanqueadora/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Cromossomos/genética , Biologia Computacional , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Gônadas/metabolismo , Imuno-Histoquímica , Fator 3 de Transcrição de Octâmero/metabolismo , Regiões Promotoras Genéticas , Análise de Sequência de Proteína , Homologia de Sequência do Ácido Nucleico , Sintenia/genéticaRESUMO
Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not encode proteins. Studies show that ncRNAs are not only involved in cell proliferation, apoptosis, differentiation, metabolism and other physiological processes, but also involved in the pathogenesis of diseases. Cardiac remodeling is the main pathological basis of a variety of cardiovascular diseases. Many studies have shown that the occurrence and development of cardiac remodeling are closely related with the regulation of ncRNAs. Recent research of ncRNAs in heart disease has achieved rapid development. Thus, we summarize here the latest research progress and mainly the molecular mechanism of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), in cardiac remodeling, aiming to look for new targets for heart disease treatment.
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Doenças Cardiovasculares/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA/genética , Remodelação Ventricular , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Humanos , MicroRNAs/metabolismo , RNA/metabolismo , RNA Circular , RNA Longo não Codificante/metabolismoRESUMO
PRDM1 (PRDI-BF1-RIZ1 homologous domain containing 1) appears to be a pleiotropic regulatory factor in various processes. It contains a PR (PRDI-BF1-RIZ1 homologous) domain protein and five zinc fingers. In the present study, a gene coding the homolog of prdm1 and the 5' regulatory region of prdm1 was identified from the Paralichthys olivaceus (denoted Po-prdm1). Results of real-time quantitative polymerase chain reaction amplification (RT-qPCR) and in situ hybridization (ISH) in embryos revealed that Po-prdm1 was highly expressed between the early gastrula and tail bud stages, with its expression peaking in the mid-gastrula stage, whereas the results of RT-qPCR and ISH in tissues demonstrated that Po-prdm1 transcripts were ubiquitously detected in all tissues, which indicates its pleiotropic function in multiple processes. ISH of gonadal tissues revealed that the transcripts were located in the nucleus and cytoplasm of the oocytes in the ovaries but only in the spermatogonia and not in the spermatocytes in the testes. The Po-prdm1 transcription factor binding sites and their conserved binding region among vertebrates were analyzed in this study. The combined results suggest that Po-PRDM1 has a conserved function in teleosts and mammals.
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Embrião não Mamífero/fisiologia , Proteínas de Peixes/metabolismo , Linguado/embriologia , Animais , Linguado/fisiologiaRESUMO
Sox3, which belongs to the SoxB1 subgroup, plays major roles in neural and gonadal development. In the present study, Japanese flounder Paralichthys olivaceus sox3 gene (Posox3) and its promoter sequence were isolated and characterized. The deduced PoSox3 protein contained 298 amino acids with a characteristic HMG-box domain. Alignment and phylogenetic analyses indicated that PoSox3 shares highly identical sequence with Sox3 homologues from different species. The promoter region of Posox3 has many potential transcription factor (TF) binding sites. The expression profiles of Posox3 in different developmental stages and diverse adult tissues were analyzed by quantitative real-time RT-PCR (qRT-PCR). Posox3 mRNA was maternally inherited, and maintained at a considerably high expression level between the blastula stage and the hatching stage during embryonic development. Posox3 was abundantly expressed in the adult brain and showed sexually dimorphic expression pattern. In situ hybridization (ISH) was carried out to investigate the cellular distribution of Posox3 in the ovary, and results showed the uniform distribution of Posox3 throughout the cytoplasm of oogonia and stage I-III oocytes. These results indicate that Posox3 has potentially vital roles in embryonic and neural development and may be involved in the oogenesis process. Our work provides a fundamental understanding of the structure and potential functions of Sox3 in Paralichthys olivaceus.
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Clonagem Molecular , Linguado/genética , Expressão Gênica , Regiões Promotoras Genéticas , Fatores de Transcrição SOXB1/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Biologia Computacional/métodos , Desenvolvimento Embrionário/genética , Linguado/classificação , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genômica/métodos , Dados de Sequência Molecular , Especificidade de Órgãos/genética , Filogenia , Fatores de Transcrição SOXB1/química , Alinhamento de SequênciaRESUMO
PRDM14 is a PR (PRDI-BF1-RIZ1 homologous) domain protein with six zinc fingers and essential roles in genome-wide epigenetic reprogramming. This protein is required for the establishment of germ cells and the maintenance of the embryonic stem cell ground state. In this study, we cloned the full-length cDNA and genomic DNA of the Paralichthys olivaceus prdm14 (Po-prdm14) gene and isolated the 5' regulatory region of Po-prdm14 by whole-genome sequencing. Peptide sequence alignment, gene structure analysis, and phylogenetic analysis revealed that Po-PRDM14 was homologous to mammalian PRDM14. Results of real-time quantitative polymerase chain reaction amplification (RT-qPCR) and in situ hybridization (ISH) in embryos demonstrated that Po-prdm14 was highly expressed between the morula and late gastrula stages, with its expression peaking in the early gastrula stage. Relatively low expression of Po-prdm14 was observed in the other developmental stages. ISH of gonadal tissues revealed that the transcripts were located in the nucleus of the oocytes in the ovaries but only in the spermatogonia and not the spermatocytes in the testes. We also presume that the Po-prdm14 transcription factor binding sites and their conserved binding region among vertebrates. The combined results suggest that Po-PRDM14 has a conserved function in teleosts and mammals.
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Linguado/genética , Proteínas Repressoras/química , Proteínas Repressoras/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Clonagem Molecular , DNA Complementar , Linguado/classificação , Regulação da Expressão Gênica , Ordem dos Genes , Loci Gênicos , Gônadas/metabolismo , Dados de Sequência Molecular , Motivos de Nucleotídeos , Filogenia , Regiões Promotoras Genéticas , Proteínas Repressoras/metabolismo , Alinhamento de Sequência , Homologia de Sequência , Sítio de Iniciação de TranscriçãoRESUMO
BACKGROUND: Corneal alkali burns can lead to ulceration, perforation, and even corneal blindness due to epithelial defects and extensive cell necrosis, resulting in poor healing outcomes. Previous studies have found that chitosan-based in situ hydrogel loaded with limbal epithelium stem cells (LESCs) has a certain reparative effect on corneal alkali burns. However, the inconsistent pore sizes of the carriers and low cell loading rates have resulted in suboptimal repair outcomes. In this study, 4D bioprinting technology was used to prepare a chitosan-based thermosensitive gel carrier (4D-CTH) with uniform pore size and adjustable shape to improve the transfer capacity of LESCs. METHODS: Prepare solutions of chitosan acetate, carboxymethyl chitosan, and ß-glycerophosphate sodium at specific concentrations, and mix them in certain proportions to create a pore-size uniform scaffold using 4D bioprinting technology. Extract and culture rat LESCs (rLESCs) in vitro, perform immunofluorescence experiments to observe the positivity rate of deltaNp63 cells for cell identification. Conduct a series of experiments to validate the cell compatibility of 4D-CTH, including CCK-8 assay to assess cell toxicity, scratch assay to evaluate the effect of 4D-CTH on rLESCs migration, and Calcein-AM/PI cell staining experiment to examine the impact of 4D-CTH on rLESCs proliferation and morphology. Establish a severe alkali burn model in rat corneas, transplant rLESCs onto the injured cornea using 4D-CTH, periodically observe corneal opacity and neovascularization using a slit lamp, and evaluate epithelial healing by fluorescein sodium staining. Assess the therapeutic effect 4D-CTH-loaded rLESCs on corneal alkali burn through histological evaluation of corneal tissue paraffin sections stained with hematoxylin and eosin, as well as immunofluorescence staining of frozen sections. RESULTS: Using the 4D-CTH, rLESCs were transferred to the alkali burn wounds of rats. Compared with the traditional treatment group (chitosan in situ hydrogel encapsulating rLESCs), the 4D-CTH-rLESC group had significantly higher repair efficiency of corneal injury, such as lower corneal opacity score (1.2 ± 0.4472 vs 0.4 ± 0.5477, p < 0.05) and neovascularization score (5.5 ± 1.118 vs 2.6 ± 0.9618, p < 0.01), and significantly higher corneal epithelial wound healing rate (72.09 ± 3.568% vs 86.60 ± 5.004%, p < 0.01). CONCLUSION: In summary, the corneas of the 4D-CTH-rLESC treatment group were similar to the normal corneas and had a complete corneal structure. These findings suggested that LESCs encapsulated by 4D-CTH significantly accelerated corneal wound healing after alkali burn and can be considered as a rapid and effective method for treating epithelial defects.
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Queimaduras Químicas , Quitosana , Lesões da Córnea , Opacidade da Córnea , Ratos , Animais , Queimaduras Químicas/tratamento farmacológico , Queimaduras Químicas/patologia , Quitosana/química , Álcalis/farmacologia , Álcalis/uso terapêutico , Cicatrização , Córnea , Lesões da Córnea/terapia , Opacidade da Córnea/patologia , Células-Tronco/patologia , Hidrogéis/farmacologiaRESUMO
During the last few decades, the morbidity and mortality of heart failure (HF) have remained on an upward trend. Despite the advances in therapeutic and diagnostic measures, there are still many aspects requiring further research. This study is aimed at finding potential long noncoding RNAs (lncRNAs) that could aid with the diagnosis and treatment of HF. We performed RNA sequencing on the peripheral blood of healthy controls as well as HF patients. The expression of lncRNAs was validated by RT-qPCR. Bioinformatic analysis was performed to investigate the possible mechanism of differentially expressed lncRNAs and mRNAs. The diagnostic value of lncRNAs was analysed by ROC analysis. Finally, a total of 207 mRNAs and 422 lncRNAs were identified. GO and KEGG pathway analyses revealed that biological pathways such as immune response, regulation of cell membrane, and transcriptional regulatory process were associated with the pathological progress of HF. The lncRNA-mRNA coexpression network was conducted, and several mRNAs were identified as key potential pathological targets, while lncRNA CHST11, MIR29B2CHG, CR381653.1, and FP236383.2 presented a potential diagnostic value for HF. These findings provide novel insights for the underlying mechanisms and possible therapeutic targets for HF.
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Insuficiência Cardíaca , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/metabolismo , Regulação da Expressão Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Biologia Computacional , Insuficiência Cardíaca/genética , Redes Reguladoras de Genes , Perfilação da Expressão GênicaRESUMO
Patients with diabetes have severe vascular complications, such as diabetic nephropathy, diabetic retinopathy, cardiovascular disease, and neuropathy. Devastating vascular complications lead to increased mortality, blindness, kidney failure, and decreased overall quality of life in people with type 2 diabetes (T2D). Glycolipid metabolism disorder plays a vital role in the vascular complications of T2D. However, the specific mechanism of action remains to be elucidated. In T2D patients, vascular damage begins to develop before insulin resistance and clinical diagnosis. Endothelial dysregulation is a significant cause of vascular complications and the early event of vascular injury. Hyperglycemia and hyperlipidemia can trigger inflammation and oxidative stress, which impair endothelial function. Furthermore, during the pathogenesis of T2D, epigenetic modifications are aberrant and activate various biological processes, resulting in endothelial dysregulation. In the present review, we provide an overview and discussion of the roles of hyperglycemia- and hyperlipidemia-induced endothelial dysfunction, inflammatory response, oxidative stress, and epigenetic modification in the pathogenesis of T2D. Understanding the connections of glucotoxicity and lipotoxicity with vascular injury may reveal a novel potential therapeutic target for diabetic vascular complications.
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Corneal fibrosis is a complication of severe corneal injury, one of the major causes of vision loss. The formation of myofibroblasts has emerged as a key stimulative factor of corneal fibrosis. In the current study, we focused on the role of LINC00963 in regulating corneal fibrosis. Transforming growth factor ß1 (TGF-ß1) was used to induce human corneal stromal cells differentiating into corneal myofibroblasts, and the significant increase of α-smooth muscle actin (α-SMA) was verified by quantitative real-time PCR (qRT-PCR), western blot, and immunofluorescence, respectively. LINC00963 was identified to be one-half decreased compared with nonstimulated human corneal stromal cells, indicating that it might play a role in corneal fibrosis. Interestingly, overexpression of LINC00963 resulted in decreased formation of myofibroblasts indicating that it might exhibit an inhibiting effect. Moreover, bioinformatics tool was applied to predict the downstream target of LINC00963. We investigated that LINC00963 suppressed α-SMA induced by TGF-ß1 in corneal fibroblasts, at least in part, by downregulating the expression of miR-143-3p. In addition, either LINC00963 promotion or miR-143-3p inhibition could significantly decrease myofibroblast contractility and collagen I and III secretion, which are the key to contribute to corneal fibrosis. Taken together, our study identified LINC00963 as a promising therapeutic target.
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Lesões da Córnea , MicroRNAs , RNA Longo não Codificante , Actinas/genética , Actinas/metabolismo , Células Cultivadas , Cicatriz/metabolismo , Lesões da Córnea/genética , Lesões da Córnea/metabolismo , Fibroblastos/metabolismo , Fibrose , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
Non-small cell lung cancer (NSCLC) is a major cause of death in those with malignant tumors. To achieve the early diagnosis of NSCLC, we investigated serum-derived Piwi-interacting RNA (piRNA) of extracellular vesicles to filter diagnostic biomarkers for NSCLC. High-throughput sequencing from cancerous tissues and adjacent noncancerous tissues in patients with NSCLC was first applied to recognize candidate piRNAs as diagnostic biomarkers. These screened piRNAs were further validated in 115 patients (including 95 cases in stage I) and 47 healthy individuals using quantitative real-time PCR (qRT-PCR). We showed that piR-hsa-164586 was significantly upregulated compared with paracancerous tissues and extracellular vesicles from the serum samples of healthy individuals. Moreover, the area under the curve (AUC) value of piR-hsa-164586 was 0.623 and 0.624 to distinguish patients with all stages or stage I of NSCLC, respectively, from healthy individuals. The diagnostic performance of piR-hsa-164586 was greatly improved compared with the cytokeratin-19-fragment (CYFRA21-1). Additionally, piR-hs-164586 was associated with the clinical characteristics of patients with NSCLC. Its expression was associated with the age and TNM stage of patients with NSCLC, indicating that it can serve as an effective and promising biomarker for the early diagnosis of NSCLC.
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Excessive production of free radicals can induce cellular damage, which is associated with many diseases. RNA is more susceptible to oxidative damage than DNA due to its single-stranded structure, and lack of protective proteins. Yet, oxidative damage to RNAs received little attention. Accumulating evidence reveals that oxidized RNAs may be dysfunctional and play fundamental role in the occurrence and development of type 2 diabetes (T2D) and its complications. Oxidized guanine nucleoside, 8-oxo-7, 8-dihydroguanine (8-oxoGuo) is a biomarker of RNA oxidation that could be associated with prognosis in patients with T2D. Nowadays, some clinical trials used antioxidants for the treatment of T2D, though the pharmacological effects remained unclear. In this review, we overview the cellular handling mechanisms and the consequences of the oxidative RNA damage for the better understanding of pathogenesis of T2D and may provide new insights to better therapeutic strategy.
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BACKGROUND: Breast invasive carcinoma (BRCA) has a poor prognosis. Numerous studies have shown that SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is involved in the initiation and progression of many cancers. This study aims to reveal the potential mechanism of SETDB1 in the development and progression of BRCA. METHODS: The ONCOMINE database, TIMER database, UALCAN database and GEPIA database were used to analyze the expression of SETDB1 in human cancers. We evaluated the expression level of SETDB1 in cell lines by quantitative real-time polymerase chain reaction (qPCR), and the survival analysis of SETDB1 was performed on PrognoScan and Kaplan-Meier plotter websites. The upstream regulator was obtained from starBase database. RESULTS: We confirmed that SETDB1 messenger RNA (mRNA) level showed high expression in breast cell lines, and we also found that SETDB1 showed high expression in many types of cancers. Moreover, SETDB1 overexpression was positively correlated with poor prognosis in BRCA. Furthermore, we first predicted miR-29a-3p was a potential upstream regulator of SETDB1 in BRCA. Our findings indicated that SETDB1 might play a carcinogenic role by increasing the infiltration of immune cell and influencing immune checkpoint expression. CONCLUSIONS: This study suggested that miR-29a-3p can mediate the expression of SETDB1 with poor prognosis and tumor immune infiltration in BRCA.
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Cardiovascular disease (CVD) is one of the most important diseases endangering human life. The pathogenesis of CVDs is complex. Pyroptosis, which differs from traditional apoptosis and necrosis, is characterized by cell swelling until membrane rupture, resulting in the release of cell contents and activation of a strong inflammatory response. Recent studies have revealed that inflammation and pyroptosis play important roles in the progression of CVDs. Noncoding RNAs (ncRNAs) are considered promising biomarkers and potential therapeutic targets for the diagnosis and treatment of various diseases, including CVDs. Growing evidence has revealed that ncRNAs can mediate the transcriptional or posttranscriptional regulation of pyroptosis-related genes by participating in the pyroptosis regulatory network. The role and molecular mechanism of pyroptosis-regulating ncRNAs in cardiovascular pathologies are attracting increasing attention. Here, we summarize research progress on pyroptosis and the role of ncRNAs, particularly microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), in the regulation of pyroptosis in CVD pathologies. Identifying these disease-related ncRNAs is important for understanding the pathogenesis of CVDs and providing new targets and ideas for their prevention and treatment.
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Cardiovascular diseases (CVDs) remain the world's leading cause of death. Cardiomyocyte autophagy helps maintain normal metabolism and functioning of the heart. Importantly, mounting evidence has revealed that autophagy plays a dual role in CVD pathology. Under physiological conditions, moderate autophagy maintains cell metabolic balance by degrading and recycling damaged organelles and proteins, and it promotes myocardial survival, but excessive or insufficient autophagy is equally deleterious and contributes to disease progression. Noncoding RNAs (ncRNAs) are a class of RNAs transcribed from the genome, but most ncRNAs do not code for functional proteins. In recent years, increasingly, various ncRNAs have been identified, and they play important regulatory roles in the physiological and pathological processes of organisms, as well as in autophagy. Thus, determining whether ncRNA-regulated autophagy plays a protective role in CVDs or promotes their progression can help us to develop ncRNAs as therapeutic targets in autophagy-related CVDs. In this review, we briefly summarize the regulatory roles of several important ncRNAs, including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), in the autophagy of various CVDs to provide a theoretical basis for the etiology and pathogenesis of CVDs and develop novel therapies to treat CVDs.
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Identifying high specificity and sensitivity biomarkers has always been the focus of research in the field of non-invasive cancer diagnosis. Exosomes are extracellular vesicles with a lipid bilayer membrane that can be released by all types of cells, which contain a variety of proteins, lipids, and a variety of non-coding RNAs. Increasing research has shown that the lipid bilayer can effectively protect the nucleic acid in exosomes. In cancers, tumor cell-derived exosomal circRNAs can act on target cells or organs through the transport of exosomes, and then participate in the regulation of tumor development and metastasis. Since exosomes exist in various body fluids and circRNAs in exosomes exhibit high stability, exosomal circRNAs have the potential as biomarkers for early and minimally invasive cancer diagnosis and prognosis judgment. In this review, we summarized circRNAs and their biological roles in cancers, with the emerging value biomarkers in cancer diagnosis, disease judgment, and prognosis observation. In addition, we briefly compared the advantages of exosomal circRNAs as biomarkers and the current obstacles in the exosome isolation technology, shed light to the future development of this technology.
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Biomarcadores Tumorais/metabolismo , Exossomos/metabolismo , Neoplasias/metabolismo , RNA Circular/metabolismo , Animais , HumanosRESUMO
Circular RNAs (circRNAs) are a large class of noncoding RNAs that are emerging as critical regulators of various cellular processes that are involved in the physiopathological mechanism of many human diseases, such as cardiovascular disease, atherosclerosis, diabetes mellitus, and carcinogenesis. Autophagy is a conserved and catabolic cellular process that degrades unfolded, misfolded, or damaged protein aggregates or organelles to maintain cellular homeostasis under physiological and pathological conditions. Increasing evidence has shown a link between circRNAs and autophagy that is closely related to the occurrence and development of human diseases, including cancer. In this review, we highlight recent advances in understanding the functions and mechanisms of circRNAs in the regulation of autophagy in cancer. These autophagy-related circRNAs contribute to cancer development and progression in various types of human cancer by activating or inhibiting autophagy. Cumulative research on the relationship between circRNAs and autophagy regulation provides critical insight into the essential role that circRNAs play in carcinogenesis and suggests new targets for tumor therapy.