RESUMEN
Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.
Asunto(s)
MicroARNs , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatología , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/fisiología , Humanos , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/fisiología , ARN Circular/genética , ARN Circular/fisiología , ARN Circular/metabolismo , Estrés Oxidativo , Apoptosis/genéticaRESUMEN
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA), and circular RNA can modulate PTEN through various pathways, thereby impacting the biological behavior of NPC. In addition, PTEN is involved in regulating the tumor microenvironment of NPC, and its interaction with the Epstein-Barr virus has also recently become a focus of research. A comprehensive understanding of the PTEN regulatory network provides a foundation for future personalized and targeted therapeutic strategies. This study expands our understanding of the pathogenesis of NPC and suggests new directions in the field of tumor biology and NPC treatment.
Asunto(s)
MicroARNs , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Fosfohidrolasa PTEN , Microambiente Tumoral , Humanos , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , MicroARNs/genética , MicroARNs/metabolismo , Microambiente Tumoral/genética , Proliferación Celular/genética , Apoptosis/genética , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Autofagia/genética , Movimiento Celular/genética , ARN Circular/genética , ARN Circular/metabolismo , ARN Circular/fisiología , Herpesvirus Humano 4/genética , Transducción de SeñalRESUMEN
The dynamic balance between bone formation and bone resorption is a critical process of bone remodeling. The imbalance of bone formation and bone resorption is closely associated with the occurrence and development of various bone-related diseases. Under both physiological and pathological conditions, non-coding RNAs (ncRNAs) play a crucial regulatory role in protein expression through either inhibiting mRNAs translation or promoting mRNAs degradation. Circular RNAs (circRNAs) are a type of non-linear ncRNAs that can resist the degradation of RNA exonucleases. There is accumulating evidence suggesting that circRNAs and microRNAs (miRNAs) serve as critical regulators of bone remodeling through their direct or indirect regulation of the expression of osteogenesis-related genes. Additionally, recent studies have revealed the involvement of the circRNAs-miRNAs regulatory network in the process by which mesenchymal stem cells (MSCs) differentiate towards the osteoblasts (OB) lineage and the process by which bone marrow-derived macrophages (BMDM) differentiate towards osteoclasts (OC). The circRNA-miRNA network plays an important regulatory role in the osteoblastic-osteoclastic balance of bone remodeling. Therefore, a thorough understanding of the circRNA-miRNA regulatory mechanisms will contribute to a better understanding of the regulatory mechanisms of the balance between osteoblastic and osteoclastic activities in the process of bone remodeling and the diagnosis and treatment of related diseases. Herein, we reviewed the functions of circRNA and microRNA. We also reviewed their roles in and the mechanisms of the circRNA-miRNA regulatory network in the process of bone remodeling. This review provides references and ideas for further research on the regulation of bone remodeling and the prevention and treatment of bone-related diseases.
Asunto(s)
Remodelación Ósea , MicroARNs , Osteoblastos , Osteogénesis , ARN Circular , Animales , Humanos , Remodelación Ósea/genética , Remodelación Ósea/fisiología , Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , MicroARNs/genética , MicroARNs/metabolismo , Osteoblastos/metabolismo , Osteoblastos/citología , Osteoclastos/metabolismo , Osteoclastos/citología , Osteogénesis/genética , Osteogénesis/fisiología , ARN Circular/genética , ARN Circular/fisiologíaRESUMEN
BACKGROUND: The mechanotransduction mechanisms by which cells regulate tissue remodeling are not fully deciphered. Circular RNAs (circRNAs) are crucial to various physiological processes, including cell cycle, differentiation, and polarization. However, the effects of mechanical force on circRNAs and the role of circRNAs in the mechanobiology of differentiation and remodeling in stretched periodontal ligament stem cells (PDLSCs) remain unclear. This article aims to explore the osteogenic function of mechanically sensitive circular RNA protein kinase D3 (circPRKD3) and elucidate its underlying mechanotransduction mechanism. MATERIALS AND METHODS: PDLSCs were elongated with 8% stretch at 0.5 Hz for 24 h using the Flexcell® FX-6000™ Tension System. CircPRKD3 was knockdown or overexpressed with lentiviral constructs or plasmids. The downstream molecules of circPRKD3 were predicted by bioinformatics analysis. The osteogenic effect of related molecules was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. RESULTS: Mechanical force enhanced the osteogenesis of PDLSCs and increased the expression of circPRKD3. Knockdown of circPRKD3 hindered PDLSCs from osteogenesis under mechanical force, while overexpression of circPRKD3 promoted the early osteogenesis process of PDLSCs. With bioinformatics analysis and multiple software predictions, we identified hsa-miR-6783-3p could act as the sponge of circPRKD3 to indirectly regulate osteogenic differentiation of mechanically stimulated PDLSCs. CONCLUSIONS: Our results first suggested that both circPRKD3 and hsa-miR-6783-3p could enhance osteogenesis of stretched PDLSCs. Furthermore, hsa-miR-6783-3p could sponge circPRKD3 to indirectly regulate RUNX2 during the periodontal tissue remodeling process in orthodontic treatment.
Asunto(s)
MicroARNs , Osteogénesis , Ligamento Periodontal , ARN Circular , Células Madre , Ligamento Periodontal/citología , Osteogénesis/genética , Osteogénesis/fisiología , Humanos , ARN Circular/genética , ARN Circular/fisiología , MicroARNs/genética , Células Madre/metabolismo , Células Cultivadas , Mecanotransducción Celular/fisiología , Diferenciación Celular/genética , Estrés Mecánico , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
Atherosclerosis (AS) is a chronic inflammatory vascular disease that begins with endothelial activation followed by a series of inflammatory responses, plaque formation, and finally rupture. An early event in endothelial dysfunction is activation of the nuclear factor-κB (NF-κB) signaling axis. Toll-like receptors (TLRs) in endothelial cells (ECs) play an essential role in recognizing pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and lifestyle-associated molecular patterns (LAMPs). Activation of the canonical NF-κB pathway stimulates the expression of cytokines, chemokines, and an array of additional genes which activate and amplify AS-associated inflammatory responses. In this review, we discuss the involvement of TLR2/4 and NF-κB signaling in ECs during AS initiation, as well as regulation of the inflammatory response during AS by noncoding RNAs, especially microRNA (miRNA) and circular RNA (circRNA).
Asunto(s)
Aterosclerosis , Células Endoteliales , FN-kappa B , Transducción de Señal , Receptor Toll-Like 2 , Receptor Toll-Like 4 , Humanos , Aterosclerosis/metabolismo , Aterosclerosis/inmunología , FN-kappa B/metabolismo , Células Endoteliales/metabolismo , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , MicroARNs/genética , MicroARNs/metabolismo , Animales , ARN Circular/genética , ARN Circular/metabolismo , ARN Circular/fisiología , Inflamación/metabolismoRESUMEN
Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated. With the deepening of research, circular RNAs (circRNAs) have been found to not only play a significant role in tumor progression and prognosis but also show aberrant expression in various tumor metastases, consequently impacting tumor metastasis through multiple pathways. Therefore, circRNAs are emerging as potential tumor markers and treatment targets. This review summarizes the research progress on elucidating how circRNAs regulate the urological cancer invasion-metastasis cascade response and related processes, as well as their role in immune microenvironment remodeling and circRNA vaccines. This body of work highlights circRNA regulation as an emerging therapeutic target for urological cancers, which should motivate further specific research in this regard.
Asunto(s)
Metástasis de la Neoplasia , ARN Circular , Neoplasias Urológicas , Humanos , ARN Circular/genética , ARN Circular/fisiología , Animales , Neoplasias Urológicas/genética , Neoplasias Urológicas/patología , Neoplasias Urológicas/terapia , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
BACKGROUND AND AIM: Circular RNA (circRNA) has been found to mediate ulcerative colitis (UC) progression by regulating intestinal mucosal barrier function. However, the role of circSOD2 in UC process and its underlying molecular mechanism still need to be further elucidated. METHODS: Lipopolysaccharide (LPS)-induced Caco2 cells were used to mimic UC cell models. CircSOD2, miR-378g, and Snail1 levels were determined by quantitative real-time PCR. Cell viability was detected using MTT assay, and inflammatory cytokine levels were measured using ELISA. The intestinal mucosal barrier function was evaluated by testing transepithelial electrical resistance and fluorescein isothiocyanate (FITC)-dextran permeability. Snail1 and tight junction-related markers (Zo-1 and Claudin2) protein levels were examined using western blot. The interaction between miR-378g and circSOD2 or Snail1 was confirmed by dual-luciferase reporter assay. Dextran sulfate sodium (DSS) was used to induce UC rat models in vivo. RESULTS: CircSOD2 was overexpressed in UC patients, and its knockdown significantly increased cell viability, transepithelial electrical resistance, and tight junction-related protein expression, while reduced inflammation cytokine levels and the permeability of FITC-dextran in LPS-induced Caco2 cells. In terms of mechanism, circSOD2 sponged miR-378g to positively regulate Snail1 expression. MiR-378g inhibitor reversed the effect of circSOD2 knockdown on intestinal mucosal barrier injury and Snail1 expression in LPS-induced Caco2 cells. In DSS-induced UC rat models, circSOD2 knockdown also could repair the intestinal mucosal barrier injury through regulating miR-378g/Snail1 axis. CONCLUSION: CircSOD2 could destroy intestinal mucosal barrier function in LPS-induced Caco2 cells and DSS-induced UC rats by miR-378g/Snail1 axis.
Asunto(s)
Colitis Ulcerosa , Mucosa Intestinal , MicroARNs , Factores de Transcripción de la Familia Snail , Factores de Transcripción de la Familia Snail/metabolismo , Factores de Transcripción de la Familia Snail/genética , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Colitis Ulcerosa/genética , Colitis Ulcerosa/patología , Colitis Ulcerosa/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Células CACO-2 , Animales , ARN Circular/genética , ARN Circular/metabolismo , ARN Circular/fisiología , Masculino , Modelos Animales de Enfermedad , Ratas , Ratas Sprague-Dawley , Lipopolisacáridos , Permeabilidad , Expresión Génica , Funcion de la Barrera IntestinalRESUMEN
Circular RNAs are a class of noncoding RNAs with covalently linked 5' and 3' ends that arise from backsplicing events. The absence of a 5' cap and a 3' poly(A) tail makes circular RNAs relatively more stable than their linear counterparts. They are evolutionary conserved and tissue-specific, and some show disease-specific expression patterns. Although their biological functions remain largely unknown, circular RNAs have been shown to play regulatory roles by acting as microRNA sponges, regulators of RNA-binding proteins, alternative splicing, and parental gene expression, and they could even encode proteins. Over the past few decades, circular RNAs have attracted wide attention in oncology owing to their implications in various tumors. Many circular RNAs have been characterized as key players in gastrointestinal cancers and influence cancer growth, progression, metastasis, and therapeutic resistance. Accumulating evidence reveals that their unique characteristics, coupled with their critical roles in tumorigenesis, make circular RNAs promising non-invasive clinical biomarkers for gastrointestinal cancers. In the present review, we summarized the biological roles of the emerging circular RNAs and their potential as biomarkers and therapeutic targets, which may help better understand their clinical significance in the management of gastrointestinal cancers.
Asunto(s)
Biomarcadores de Tumor , Neoplasias Gastrointestinales , ARN Circular , ARN , Humanos , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/terapia , Neoplasias Gastrointestinales/patología , ARN Circular/genética , ARN Circular/fisiología , ARN Circular/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , ARN/genética , Terapia Molecular Dirigida , MicroARNs/genética , MicroARNs/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Empalme Alternativo/genética , Progresión de la EnfermedadRESUMEN
PROBLEM: Preeclampsia (PE) is an obstetric disease involving multiple systems, which account for maternal and fetal complications and increased mortality. Circular RNAs (circRNAs) were recently deemed to associate with the pathogenesis of PE. This study aims to clarify the correlation between circRNA hsa_circ_0001326 and PE and explore its biological function in PE. METHOD OF STUDY: The expression of hsa_circ_0001326 in PE placentas was detected by real-time quantitative PCR (qRT-PCR). After overexpressing or inhibiting hsa_circ_0001326 in trophoblast cells, the cell growth, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assays. Western blot assay was applied to detect the epithelial-mesenchymal transition (EMT) proteins, E-cadherin and Vimentin. Furthermore, a dual-luciferase reporter assay was applied to verify the binding sites of hsa_circ_0001326, miR-145-5p, and transforming growth factor beta 2 (TGFB2). RESULTS: Hsa_circ_0001326 was found to be higher expressed in PE placentas than in normal placentas. Furthermore, hsa_circ_0001326 played a negative regulating role in trophoblast cell viability, migration, and invasion. Overexpression of hsa_circ_0001326 inhibited the viability, migration, and invasion of trophoblast cells, while inhibition of hsa_circ_0001326 showed opposite effects. Mechanistically, hsa_circ_0001326 sponged miR-145-5p to elevate TGFB2 expression in trophoblast cells. CONCLUSION: This study provided evidence that the up-regulated hsa_circ_0001326 in PE restrained trophoblast cells proliferation, migration, and invasion by sponging miR-145-5p to elevate TGFB2 expression. Our results might provide a novel insight into the role of hsa_circ_0001326 in the pathogenesis of PE.
Asunto(s)
MicroARNs , ARN Circular , Factor de Crecimiento Transformador beta2 , Trofoblastos , Femenino , Humanos , Embarazo , Western Blotting , Movimiento Celular , Proliferación Celular , MicroARNs/genética , Placenta/metabolismo , Placenta/fisiología , ARN Circular/genética , ARN Circular/fisiología , Factor de Crecimiento Transformador beta2/genética , Trofoblastos/citología , Trofoblastos/metabolismo , Trofoblastos/fisiologíaRESUMEN
Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-ß-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention.
Asunto(s)
Senescencia Celular , MicroARNs , ARN Circular , Animales , Proliferación Celular/genética , Senescencia Celular/genética , Fibroblastos/metabolismo , Ratones , MicroARNs/genética , MicroARNs/fisiología , ARN Circular/genética , ARN Circular/fisiologíaRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. The mechanism by which circular RNA (circRNA) drives PCOS development remains unclear. Thus, the study is designed to explore the role of a novel circRNA, circ_FURIN, in the PCOS cell model and the underlying mechanism. METHODS: PCOS cell model was established by treating human ovarian granulosa-like tumor cells (KGN) with Testosterone (TTR). RNA expressions of circ_FURIN, microRNA-423-5p (miR-423-5p) and myotubularin 1 (MTM1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was checked by Western blot. Cell proliferation was investigated by a 5-Ethynyl-29-deoxyuridine assay, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis for cell cycle. Apoptotic cells were quantified by flow cytometry analysis for cell apoptosis. The interplay between miR-423-5p and circ_FURIN or MTM1 was identified by dual-luciferase reporter and RNA pull-down assays. RESULTS: Circ_FURIN and MTM1 expressions were significantly upregulated, whereas miR-423-5p was downregulated in the ovarian cortex tissues of PCOS patients and TTR-treated KGN cells compared with controls. Circ_FURIN depletion relieved TTR-induced proliferation inhibition and apoptosis promotion. Besides, knockdown of miR-423-5p, a target miRNA of circ_FURIN, rescued circ_FURIN knockdown-mediated effects under TTR treatment. MiR-423-5p remitted TTR-induced cell disorders by binding to MTM1. Moreover, circ_FURIN modulated MTM1 expression through miR-423-5p. CONCLUSION: Circ_FURIN silencing protected against TTR-induced dysfunction by the miR-423-5p/MTM1 pathway in human ovarian granulosa-like tumor cells.
Asunto(s)
Tumor de Células de la Granulosa/genética , MicroARNs/genética , Síndrome del Ovario Poliquístico/genética , Proteínas Tirosina Fosfatasas no Receptoras/genética , ARN Circular/genética , Apoptosis/genética , Proliferación Celular/genética , Células Cultivadas , Femenino , Furina/genética , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Tumor de Células de la Granulosa/inducido químicamente , Tumor de Células de la Granulosa/patología , Humanos , Modelos Biológicos , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patología , ARN Circular/fisiología , Testosterona/efectos adversosRESUMEN
The SQUAMOSA promoter-binding protein-like (SPL) family play a key role in guiding the switch of plant growth from juvenile to adult phases. Populus euphratica Oliv. exhibit typical heterophylly, and is therefore an ideal model for studying leaf shape development. To investigate the role and regulated networks of SPLs in the morphogenesis of P. euphratica heteromorphic leaves. In this study, 33 P. euphratica SPL (PeuSPL) genes were identified from P. euphratica genome and transcriptome data. Phylogenetic analysis depicted the classification of these SPL genes into two subgroups. The expression profiles and regulatory networks of P. euphratica SPL genes analysis displayed that major P. euphratica SPL family members gradually increases from linear to broad-ovate leaves, and they were involved in the morphogenesis regulation, stress response, transition from vegetative to reproductive growth, photoperiod, and photosynthesis etc. 14 circRNAs, and 33 lncRNAs can promote the expression of 12 of the P. euphratica SPLs by co-decoying miR156 in heteromorphic leaf morphogenesis. However, it was found that the effect of PeuSPL2-4 and PeuSPL9 in leaf shape development was contrasting to their homologous genes of Arabidopsis. Therefore, it was suggested that the SPL family were evolutionarily conserved for regulation growth, but were varies in different plant for regulation of the organ development.
Asunto(s)
Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Genes de Plantas/genética , Morfogénesis/genética , Hojas de la Planta/genética , Populus/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Fotosíntesis/genética , Filogenia , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/fisiología , Populus/crecimiento & desarrollo , Populus/fisiología , ARN Circular/fisiología , ARN Largo no Codificante/fisiología , ARN de Planta/fisiologíaRESUMEN
Acute myocardial infarction (AMI) is characterized by high morbidity and mortality rates. Circular RNAs collectively participate in the initiation and development of AMI. The purpose of this study was to investigate the role of circRbms1 in AMI. Ischemia-reperfusion (I/R) was performed to establish an AMI model. RT-qPCR and Western blotting were performed to detect mRNA and analyze protein expression, respectively. The interaction between miR-92a and circRbms1/BCL2L11 was confirmed by luciferase and RNA pull-down assays. circRbms1 is overexpressed in AMI. However, circRbms1 knockdown alleviated H9c2 cell apoptosis and reduced the release of reactive oxygen species. circRbms1 targeted miR-92a, the downregulation of which alleviated the effects of circRbms1 knockdown and increased oxidative stress and H9c2 cell apoptosis. Moreover, circRbms1 sponged miR-92a to upregulate BCL2L11, which modulated the expression of apoptosis-related genes. circRbms1 participated in myocardial I/R injury by regulating the miR-92a/BCL2L11 signaling pathway, which may provide a new strategy for the treatment of AMI.
Asunto(s)
Daño por Reperfusión Miocárdica/genética , ARN Circular/fisiología , Animales , Apoptosis/genética , Proteína 11 Similar a Bcl2/genética , Proteína 11 Similar a Bcl2/metabolismo , Células Cultivadas , Proteínas de Unión al ADN/genética , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Regulación de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/fisiología , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/genética , Proteínas de Unión al ARN/genética , Transducción de Señal/genéticaRESUMEN
CircRNA circ-PRDM5 (PR/SET domain 5) (circ-PRDM5) is overexpressed in age-related cataracts. Nevertheless, the biological role of circ-PRDM5 in posterior capsule opacities (PCO) (a common complication after cataract surgery) is unclear. Human lens epithelial cells SRA01/04 (LECs) were stimulated with TGF-ß2 (transforming growth factor beta-2) to mimic the PCO model in vitro. Cell viability, migration, and invasion were determined by MTT, transwell, or wound-healing assays. Protein levels of EMT (epithelial-to-mesenchymal transition) markers and COL1A2 (collagen type I alpha 2 chain) were analyzed by western blotting (WB). Relative expression of circ-PRDM5, miR-92b-3p, and COL1A2 mRNA was analyzed by qRT-PCR. The targeting relationship was confirmed by dual-luciferase reporter and RIP assays. We observed that circ-PRDM5 and COL1A2 were upregulated in PCO tissues and TGF-ß2-treated LECs, while miR-92b-3p was downregulated. Both circ-PRDM5 and COL1A2 knockdown impaired TGF-ß2-induced LEC migration, invasion, and EMT. Also, circ-PRDM5 could adsorb miR-92b-3p to regulate COL1A2 expression. Furthermore, miR-92b-3p inhibitor offset circ-PRDM5 knockdown-mediated influence on migration, invasion, and EMT of LECs under TGF-ß2 stimulation. Also, COL1A2 overexpression overturned the repressive influence of miR-92b-3p mimic on TGF-ß2-induced LEC migration, invasion, and EMT. In summary, TGF-ß2-induced circ-PRDM5 facilitated LEC migration, invasion, and EMT by adsorbing miR-92b-3p and increasing COL1A2 expression, offering new insights into the development of PCO.
Asunto(s)
Cristalino , MicroARNs , ARN Circular , Movimiento Celular/genética , Proliferación Celular , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/genética , Humanos , Cristalino/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/biosíntesis , ARN Circular/fisiología , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta2/farmacologíaRESUMEN
BACKGROUND: The role of estrogen receptor ß (ERß) in the pathogenesis and development of breast cancer (BC) is controversial, and it is currently considered to play contradictory roles in different phenotypes. ERß2 is thought to promote the BC process, but its role in triple-negative breast cancer (TNBC) has not been reported. METHODS: In this study, we collected tumor tissues from 15 patients with TNBC and obtained a variety of TNBC cell lines as research objects. The plasmid vectors and RNA interference techniques were used to change the level of target genes in cells, quantitative PCR and Western Blots were used to detect gene expression levels, CCK-8 and EdU assay were used to detect cell growth, and Transwell was used to detect cell migration and invasion. Dual-luciferase gene reports and RNA immunoprecipitation (RIP) were used to verify gene targeting relationships. RESULTS: ERß2 was up-regulated in TNBC tissues and promoted the growth, migration, and invasion of TNBC cells. ERß2 regulated hsa_circ_0000732 expression by binding to SCARF1 promoter. Knockdown of hsa_circ_0000732 inhibited TNBC cell proliferation, migration, and invasion by upregulating miR-1184. CONCLUSION: Our present study found that ERß2 is upregulated in some TNBC cells and promotes TNBC cell growth, migration and invasion by regulating hsa_circ_0000732 targeting miR-1184. The special role of ERß2 in TNBC may be the breakthrough of a targeted treatment strategy for TNBC.
Asunto(s)
Receptor beta de Estrógeno/fisiología , MicroARNs/fisiología , ARN Circular/fisiología , Neoplasias de la Mama Triple Negativas/etiología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Invasividad Neoplásica , Regiones Promotoras Genéticas , Receptores Depuradores de Clase F/genética , Neoplasias de la Mama Triple Negativas/patología , Regulación hacia ArribaRESUMEN
Circular RNAs (circRNAs) are key regulators in the development of many cancers. The present study was aimed to investigate the mechanism by which circ_0007919 affected colorectal cancer (CRC) progression.The differentially expressed circRNA was screened out by analyzing the expression profile of circRNAs of CRC tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for detecting the expressions of circ_0007919, miR-942-5p, and ten-eleven translocation 1 (TET1) mRNA in CRC tissues and cell lines. Cell growth and migration were assessed by cell counting kit-8 (CCK-8) 5-bromo-2'-deoxyuridine (BrdU) and scratch assays. Bioinformatics analysis and dual-luciferase reporter assay were conducted to predict and validate the targeted relationships between circ_0007919 and miR-942-5p, as well as between miR-942-5p and TET1 mRNA. Besides, Western blot was conducted for detecting TET1 protein expression in CRC cells. It was revealed that, in CRC tissues and cell lines, circ_0007919 and TET1 expressions were reduced whereas miR-942-5p expression was enhanced. It was also revealed that circ_0007919 overexpression markedly suppressed CRC cell growth and migration. In addition, circ_0007919 could competitively bind with miR-942-5p to increase the expression of miR-942-5p's target gene TET1. Collectively, circ_0007919 inhibits CRC cell growth and migration via regulating the miR-942-5p/TET1 axis. This study helps to better understand the molecular mechanism of CRC progression.
Asunto(s)
Neoplasias Colorrectales/etiología , MicroARNs/fisiología , Oxigenasas de Función Mixta/fisiología , Proteínas Proto-Oncogénicas/fisiología , ARN Circular/fisiología , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Células Tumorales CultivadasRESUMEN
The discovery of introns over four decades ago revealed a new vision of genes and their interrupted arrangement. Throughout the years, it has appeared that introns play essential roles in the regulation of gene expression. Unique processing of excised introns through the formation of lariats suggests a widespread role for these molecules in the structure and function of cells. In addition to rapid destruction, these lariats may linger on in the nucleus or may even be exported to the cytoplasm, where they remain stable circular RNAs (circRNAs). Alternative splicing (AS) is a source of diversity in mature transcripts harboring retained introns (RI-mRNAs). Such RNAs may contain one or more entire retained intron(s) (RIs), but they may also have intron fragments resulting from sequential excision of smaller subfragments via recursive splicing (RS), which is characteristic of long introns. There are many potential fates of RI-mRNAs, including their downregulation via nuclear and cytoplasmic surveillance systems and the generation of new protein isoforms with potentially different functions. Various reports have linked the presence of such unprocessed transcripts in mammals to important roles in normal development and in disease-related conditions. In certain human neurological-neuromuscular disorders, including myotonic dystrophy type 2 (DM2), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and Duchenne muscular dystrophy (DMD), peculiar processing of long introns has been identified and is associated with their pathogenic effects. In this review, we discuss different mechanisms involved in the processing of introns during AS and the functions of these large sections of the genome in our biology.
Asunto(s)
Empalme Alternativo , Enfermedad/genética , Expresión Génica , Intrones , ARN Circular/fisiología , ARN Mensajero/fisiología , Esclerosis Amiotrófica Lateral/genética , Animales , Núcleo Celular/genética , Demencia Frontotemporal/genética , Humanos , Mamíferos/genética , Distrofia Muscular de Duchenne/genética , Distrofia Miotónica/genéticaRESUMEN
Circular RNAs (circRNAs) are non-coding RNAs with closed ends which makes them resistant to degrading enzyme RNAse R. These RNA molecules show cell, tissue or organ specific expression. Regulatory functions have been reported for a number of circRNAs. Particularly, they have been found to affect cell cycle and control cell proliferation. CircRNAs are involved in physiological processes like natural organ development. Their dysregulation in high-throughput technologies have been shown in a growing number of diseases especially many types of cancers such as renal cell carcinoma (RCC). Differentially expressed circRNAs in RCC tissues compared to normal tissues may affect carcinogenesis process. Overexpressed circRNAs promote tumorigenic functions of RCC cell lines while down-regulated transcripts repress them. Both dysregulated circRNAs are correlated with clinicopathological features, prognosis and survival in RCC patients which along with their acceptable diagnostic values suggest them as potential biomarkers in diagnosis or prediction of prognosis of RCC patients. In this review, we have assessed tumorigenic or tumor-suppressing effects of circRNAs and also their diagnostic and prognostic potentials in RCC.
Asunto(s)
Carcinogénesis/genética , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , ARN Circular/fisiología , Carcinoma de Células Renales/mortalidad , Humanos , Neoplasias Renales/mortalidad , Tasa de SupervivenciaRESUMEN
The type of myofiber is related to the quality of meat. The slow oxidized myofiber helps to increase the tenderness and juiciness of muscle. Numerous studies have shown that circRNA plays a key role in skeletal muscle development. However, the role of circRNA in porcine skeletal myofiber types is unclear. In this study, we performed high-throughput RNA sequencing to study the differential expression of circRNA in the longissimus dorsi and the soleus muscle. A total of 40,757 circRNAs were identified, of which 181 were significantly different. Interestingly, some circRNAs were involved in metabolism pathways, AMPK, FoxO, and PI3K-Akt signaling pathways. Besides, we focused on a novel circRNA-circMYLK4. By injecting circMYLK4-AAV into piglets, we found that circMYLK4 significantly increased the mRNA and protein levels of the slow muscle marker genes. In summary, our study laid an essential foundation for further research of circRNA in myofiber type conversion and higher meat quality.
Asunto(s)
Desarrollo de Músculos/genética , Músculo Esquelético/crecimiento & desarrollo , ARN Circular/fisiología , Porcinos , Animales , Animales Modificados Genéticamente , Diferenciación Celular/genética , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Masculino , Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Músculo Esquelético/fisiología , ARN Circular/análisis , ARN Circular/genética , Porcinos/genética , Porcinos/crecimiento & desarrolloRESUMEN
Studies have confirmed that circular RNA (circRNA) has a stable closed structure, which plays an important role in the progression of tumors. Cancers with positive fusion genes can produce associated fusion circRNA (F-cirRNA). However, there are no reports concerning a role for F-circRNA of the echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase variant 1 (EML4-ALK1) in non-small cell lung cancer (NSCLC). Our study confirmed the existence of fusion circEA1 (F-circEA1) in NCI-H3122 cells (carrying the EML4-ALK1 gene), F-circEA1 was expressed both in the cytoplasm and nucleus as determined by fluorescence in situ hybridization (FISH) and Sanger sequencing. CCK8 and transwell assays showed that F-circEA1 was beneficial to cell proliferation, metastasis, and invasion. Overexpression of F-circEA1 can also promote cell proliferation, migration and invasion in A549 and SPCA1 cells (non-small cell lung cancer cell line not carrying the EML4-ALK1 gene). Interference with F-circEA1, induced cell cycle arrest and promoted apoptosis as determined by flow cytometry, and increased drug sensitivity to crizotinib in H3122 cells. F-circEA1 directly affected the expression of parental gene EML4-ALK1. Further research found that F-circEA1 can affect the downstream signaling pathway of ALK. In vivo, the growth rate of xenogeneic tumors was reduced and the protein expression level of EML4-ALK1 was significantly decreased in transplanted tumors measured by immunohistochemistry (IHC) after interference with F-circEA1. In conclusion, F-circEA1 can be considered as a proto-oncogene that regulates cell proliferation and apoptosis by affecting the expression of the parental gene EML4-ALK1 and its ALK downstream signaling pathway in non-small cell lung cancer.