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1.
Pathol Res Pract ; 260: 155457, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-39018926

RESUMO

5-Fluorouracil (5-FU) is a well-known chemotherapy drug extensively used in the treatment of breast cancer. It works by inhibiting cancer cell proliferation and inducing cell death through direct incorporation into DNA and RNA via thymidylate synthase (TS). Circular RNAs (circRNAs), a novel family of endogenous non-coding RNAs (ncRNAs) with limited protein-coding potential, contribute to 5-FU resistance. Their identification and targeting are crucial for enhancing chemosensitivity. CircRNAs can regulate tumor formation and invasion by adhering to microRNAs (miRNAs) and interacting with RNA-binding proteins, regulating transcription and translation. MiRNAs can influence enzymes responsible for 5-FU metabolism in cancer cells, affecting their sensitivity or resistance to the drug. In the context of 5-FU resistance, circRNAs can target miRNAs and regulate biological processes such as cell proliferation, cell death, glucose metabolism, hypoxia, epithelial-to-mesenchymal transition (EMT), and drug efflux. This review focuses on the function of circRNAs in 5-FU resistance, discussing the underlying molecular pathways and biological mechanisms. It also presents recent circRNA/miRNA-targeted cancer therapeutic strategies for future clinical application.

2.
Int J Gen Med ; 17: 2967-2979, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006913

RESUMO

Background: Relapsed/refractory acute myeloid leukemia (R/R-AML) has dismal prognosis due to chemotherapy resistance. Circular RNAs (circRNAs) have shown emerging roles in chemotherapy resistance in various cancers including hematologic malignancies. However, the potential roles of circRNAs in AML progression and drug resistance remain largely undetermined. Methods: In this study, circulating circRNAs expression profiles were analyzed among R/R-AML, de novo AML and healthy controls (HC) using a human circRNA Array. Bioinformatic analysis was carried out to explore the differentially expressed circRNAs (DE-circRNAs). GO, KEGG pathway analysis, along with circRNA-miRNA-mRNA network analysis, were conducted to identify the potential biological pathways involved in R/R-AML. Finally, the UALCAN database was used to assess the prognosis of different target DE-circRNAs-related mRNAs. Results: Forty-eight DE-circRNAs were upregulated, whereas twenty-seven DE-circRNAs were downregulated in R/R-AML samples. Up-regulated DE-circRNAs in R/R-AML samples were mainly enrichment in the biological processes and pathways of cell migration, microRNAs in cancers, Rap1 and Ras signaling pathways. Six DE-circRNAs were randomly selected to further explore their relationships with R/R-AML. GO and KEGG pathway analyses of the six candidate DE-circRNAs-related target mRNAs were mainly involved in the regulation of signal transduction and Ras signaling pathway. By overlapping our RNA-sequencing results of differentially expressed genes (DEGs) in R/R-AML samples with the candidate DE-circRNAs-predicted target mRNAs, we identified sixty-eight overlapping targeted mRNAs. Using UALCAN database analysis, we identified that AML patients with six upregulated DE-circRNA-related genes (ECE1, PI4K2A, SLC9A6, CCND3, PPP1R16B, and TRIM32) and one downregulated gene DE-circRNA-related genes (ARHGAP10) might have a poor prognosis. Conclusion: This study revealed the overall alterations of circRNAs in R/R-AML. DE-circRNAs and their related genes might be used as potential early, sensitive and stable biomarkers for AML diagnosis, R/R-AML monitoring, and even as novel treatment targets for R/R-AML.

3.
Front Genet ; 15: 1396720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978876

RESUMO

Introduction: Middle ear cholesteatoma is a chronic middle ear disease characterized by severe hearing loss and adjacent bone erosion, resulting in numerous complications. This study sought to identify pathways involved in N6-methyladenosine (m6A) modification of circRNA in middle ear cholesteatoma. Methods: A m6A circRNA epitranscriptomic microarray analysis was performed in middle ear cholesteatoma tissues (n = 5) and normal post-auricular skin samples (n = 5). Bioinformatics analyses subsequently explored the biological functions (Gene Ontology, GO) and signaling pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG) underlying middle ear cholesteatoma pathogenesis. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was performed to verify the presence of circRNAs with m6A modifications in middle ear cholesteatoma and normal skin samples. Results: Microarray analysis identified 3,755 circRNAs as significantly differentially modified by m6A methylation in middle ear cholesteatoma compared with the normal post-auricular skin. Among these, 3,742 were hypermethylated (FC ≥ 2, FDR < 0.05) and 13 were hypomethylated (FC ≤ 1/2, FDR < 0.05). GO analysis terms with the highest enrichment score were localization, cytoplasm, and ATP-dependent activity for biological processes, cellular components, and molecular functions respectively. Of the eight hypermethylated circRNA pathways, RNA degradation pathway has the highest enrichment score. Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathway was hypomethylated. To validate the microarray analysis, we conducted MeRIP-qPCR to assess the methylation levels of five specific m6A-modified circRNAs: hsa_circRNA_061554, hsa_circRNA_001454, hsa_circRNA_031526, hsa_circRNA_100833, and hsa_circRNA_022382. The validation was highly consistent with the findings from the microarray analysis. Conclusion: Our study firstly presents m6A modification patterns of circRNAs in middle ear cholesteatoma. This finding suggests a direction for circRNA m6A modification research in the etiology of cholesteatoma and provides potential therapeutic targets for the treatment of middle ear cholesteatoma.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38982736

RESUMO

Circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression. This study aimed to investigate the role and molecular mechanisms of circMYO1C in OA. CircMYO1C was upregulated in OA- and interleukin-1ß (IL-1ß)-exposed chondrocytes. The results indicated that circMYO1C knockdown repressed the inflammatory factors (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], interleukin-8 [IL-8], etc.) and apoptosis of chondrocytes following IL-1ß exposure. CircMYO1C was an N6-methyladenosine (m6A)-modified circRNA with m6A characteristics. High mobility group box 1 (HMGB1) was a target of circMYO1C. IL-1ß exposure increased the stability and half-life (t1/2) of HMGB1 mRNA, while silencing circMYO1C reduced HMGB1 mRNA stability. Taken together, circMYO1C targets the m6A/HMGB1 axis to promote chondrocyte apoptosis and inflammation. The present study demonstrates that the circMYO1C/m6A/HMGB1 axis is essential for OA progression, highlighting a novel potential therapeutic target for clinical OA.

5.
Ageing Res Rev ; 99: 102404, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38971322

RESUMO

Osteoarthritis (OA) is a chronic degenerative joint disease with multiple causative factors such as aging, mechanical injury, and obesity. Autophagy is a complex dynamic process that is involved in the degradation and modification of intracellular proteins and organelles under different pathophysiological conditions. Autophagy, as a cell survival mechanism under various stress conditions, plays a key role in regulating chondrocyte life cycle metabolism and cellular homeostasis. Non-coding RNAs (ncRNAs) are heterogeneous transcripts that do not possess protein-coding functions, but they can act as effective post-transcriptional and epigenetic regulators of gene and protein expression, thus participating in numerous fundamental biological processes. Increasing evidence suggests that ncRNAs, autophagy, and their crosstalk play crucial roles in OA pathogenesis. Therefore, we summarized the complex role of autophagy in OA chondrocytes and focused on the regulatory role of ncRNAs in OA-associated autophagy to elucidate the complex pathological mechanisms of the ncRNA-autophagy network in the development of OA, thus providing new research targets for the clinical diagnosis and treatment of OA.


Assuntos
Autofagia , Condrócitos , Osteoartrite , RNA não Traduzido , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Condrócitos/metabolismo , Condrócitos/patologia , Humanos , Autofagia/fisiologia , Autofagia/genética , RNA não Traduzido/genética , Animais
6.
Mol Neurobiol ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023794

RESUMO

Chemotherapy and radiotherapy are widely used in clinical practice across the globe as cancer treatments. Intrinsic or acquired chemoresistance poses a significant problem for medical practitioners and researchers, causing tumor recurrence and metastasis. The most dangerous kind of malignant brain tumor is called glioblastoma multiforme (GBM) that often recurs following surgery. The most often used medication for treating GBM is temozolomide chemotherapy; however, most patients eventually become resistant. Researchers are studying preclinical models that accurately reflect human disease and can be used to speed up drug development to overcome chemoresistance in GBM. Non-coding RNAs (ncRNAs) have been shown to be substantial in regulating tumor development and facilitating treatment resistance in several cancers, such as GBM. In this work, we mentioned the mechanisms of how different ncRNAs (microRNAs, long non-coding RNAs, circular RNAs) can regulate temozolomide chemosensitivity in GBM. We also address the role of these ncRNAs encapsulated inside secreted exosomes.

7.
Oncol Res ; 32(6): 1129-1139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827325

RESUMO

Circular RNAs (circRNAs) have been recognized as pivotal regulators in tumorigenesis, yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma (HCC) remain elusive. We sought to unveil the expression profile and biological role of circMYBL2 in HCC. Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells, and qRT‒PCR analysis was then performed in HCC cell lines and tissues, revealing significant upregulation of circMYBL2. Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression. Furthermore, bioinformatics analysis, qRT‒PCR analysis, luciferase reporter assays, and western blot analysis were employed to investigate the interplay among circMYBL2, miR-1205, and E2F1. CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines. Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells, whereas circMYBL2 knockdown elicited contrasting effects. Mechanistically, our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205. Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis, suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.


Assuntos
Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Progressão da Doença , Fator de Transcrição E2F1 , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs , RNA Circular , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , RNA Circular/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , MicroRNAs/genética , Movimento Celular/genética , Camundongos , Prognóstico
8.
Front Genet ; 15: 1405715, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933921

RESUMO

In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein-protein interaction networks, mRNA-lncRNA co-expression networks, and circRNA-microRNA-mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.

9.
Front Genet ; 15: 1376721, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933922

RESUMO

Background: Circular RNAs (circRNAs) play an important role in the occurrence and development of diseases. However, the role of circRNAs in male smokers with chronic obstructive pulmonary disease (COPD) remains unclear. Methods: Stable COPD patients and healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were extracted. After high-throughput RNA sequencing (RNA-Seq) of PBMCs, a bioinformatics method was used to analyse differentially expressed (DE) circRNAs (DEcircRNAs) and mRNAs (DEmRNAs). Results: Total of 114 DEcircRNAs and 58 DEmRNAs were identified. Functional enrichment analysis showed that processes related to COPD include the regulation of interleukin (IL)-18, IL-5 and the NLRP3 inflammasome; differentiation of T helper type 1 (Th1), Th2, and Th17 cells, and the AMPK, Wnt, JAK-STAT, and PI3K-Akt signalling pathways. In the protein-protein interaction (PPI) network, the core genes were MYO16, MYL4, SCN4A, NRCAM, HMCN1, MYOM2, and IQSEC3. Small-molecule prediction results revealed potential drugs for the COPD treatment. Additionally, the circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory network was constructed. Conclusion: This study identified a set of dysregulated circRNAs and mRNAs and revealed potentially important genes, pathways, new small-molecule drugs and ceRNA regulatory networks in male smokers with COPD. These circRNAs might be prospective biomarkers or potential molecular targets of the ceRNA mechanism for COPD.

10.
Cells ; 13(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38920630

RESUMO

Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression with diverse roles in various biological processes. In recent years, research into circRNAs' involvement in bone biology has gained significant attention, unveiling their potential as novel regulators and biomarkers in bone-related disorders and diseases. CircRNAs, characterized by their closed-loop structure, exhibit stability and resistance to degradation, underscoring their functional significance. In bone tissue, circRNAs are involved in critical processes such as osteogenic differentiation, osteoclastogenesis, and bone remodeling through intricate molecular mechanisms including microRNA regulation. Dysregulated circRNAs are associated with various bone disorders, suggesting their potential as diagnostic and prognostic biomarkers. The therapeutic targeting of these circRNAs holds promise for addressing bone-related conditions, offering new perspectives for precision medicine. Thus, circRNAs constitute integral components of bone regulatory networks, impacting both physiological bone homeostasis and pathological conditions. This review provides a comprehensive overview of circRNAs in bone biology, emphasizing their regulatory mechanisms, functional implications, and therapeutic potential.


Assuntos
Osso e Ossos , RNA Circular , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Osso e Ossos/metabolismo , Animais , Doenças Ósseas/genética , Doenças Ósseas/metabolismo , Osteogênese/genética , Biomarcadores/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação da Expressão Gênica
11.
Front Endocrinol (Lausanne) ; 15: 1422599, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832352

RESUMO

RNA biology has revolutionized cancer understanding and treatment, especially in endocrine-related malignancies. This editorial highlights RNA's crucial role in cancer progression, emphasizing its influence on tumor heterogeneity and behavior. Processes like alternative splicing and noncoding RNA regulation shape cancer biology, with microRNAs, long noncoding RNAs, and circular RNAs orchestrating gene expression dynamics. Aberrant RNA signatures hold promise as diagnostic and prognostic biomarkers in endocrine-related cancers. Recent findings, such as aberrant PI3Kδ splice isoforms and epithelial-mesenchymal transition-related lncRNA signatures, unveil potential therapeutic targets for personalized treatments. Insights into m6A-associated lncRNA prognostic models and the function of lncRNA LINC00659 in gastric cancer represents ongoing research in this field. As understanding of RNA's role in cancer expands, personalized therapies offer transformative potential in managing endocrine-related malignancies. This signifies a significant stride towards precision oncology, fostering innovation for more effective cancer care.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , MicroRNAs/genética , Medicina de Precisão/métodos , RNA/genética , RNA Circular/genética , Animais
12.
Int J Mol Sci ; 25(12)2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38928088

RESUMO

T lymphocytes play a critical role in antitumor immunity, but their exhaustion poses a significant challenge for immune evasion by malignant cells. Circular RNAs (circRNAs), characterized by their covalently closed looped structure, have emerged as pivotal regulators within the neoplastic landscape. Recent studies have highlighted their multifaceted roles in cellular processes, including gene expression modulation and protein function regulation, which are often disrupted in cancer. In this review, we systematically explore the intricate interplay between circRNAs and T cell modulation within the tumor microenvironment. By dissecting the regulatory mechanisms through which circRNAs impact T cell exhaustion, we aim to uncover pathways crucial for immune evasion and T cell dysfunction. These insights can inform innovative immunotherapeutic strategies targeting circRNA-mediated molecular pathways. Additionally, we discuss the translational potential of circRNAs as biomarkers for therapeutic response prediction and as intervention targets. Our comprehensive analysis aims to enhance the understanding of immune evasion dynamics in the tumor microenvironment by facilitating the development of precision immunotherapy.


Assuntos
Neoplasias , RNA Circular , Linfócitos T , Microambiente Tumoral , Humanos , RNA Circular/genética , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/terapia , Neoplasias/patologia , Neoplasias/metabolismo , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo , Regulação Neoplásica da Expressão Gênica , Imunoterapia/métodos , Animais , Biomarcadores Tumorais/genética
13.
Am J Cancer Res ; 14(5): 2228-2239, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859827

RESUMO

Circular RNAs are considered to play important roles in the progression of different cancers such as esophageal squamous cell carcinoma. However, the functions of circular RNAs in esophageal squamous cell carcinoma are still not clear. This study aimed to investigate the role and mechanism of circRNA-0036474 in the progression of esophageal squamous cell carcinoma. The hsa_circ_0036474 expression levels were found to be elevated in both EC109 cells and esophageal squamous cell carcinoma tissue samples. Moreover, knockdown of circRNA-0036474 expression in the EC109 cells induced migration and invasion, characterized by the down-regulation of E-cadherin, and up-regulation of N-cadherin and vimentin. In addition, the over-expressed hsa_circ_0036474 significantly decreased the activity of EC109 cells, elevated E-cadherin expression but declined N-cadherin and vimentin expression. Moreover, over-expressed mir-223-3p levels and interfered RERG expression verified the role of hsa_circ_0036474 in inhibiting the invasion and migration of EC109 cells, reducing the expression of N-cadherin and vimentin, and promoting the expression of E-cadherin. In conclusion, circRNA-0036474 mitigated the progression of esophageal squamous cell carcinoma through regulating mir-223-3p/RERG axis, presenting a potential therapeutic target for the treatment.

14.
Br J Pharmacol ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830749

RESUMO

Cardiac remodelling involves structural, cellular and molecular alterations in the heart after injury, resulting in progressive loss of heart function and ultimately leading to heart failure. Circular RNAs (circRNAs) are a recently rediscovered class of non-coding RNAs that play regulatory roles in the pathogenesis of cardiovascular diseases, including heart failure. Thus, a more comprehensive understanding of the role of circRNAs in the processes governing cardiac remodelling may set the ground for the development of circRNA-based diagnostic and therapeutic strategies. In this review, the current knowledge about circRNA origin, conservation, characteristics and function is summarized. Bioinformatics and wet-lab methods used in circRNA research are discussed. The regulatory function of circRNAs in cardiac remodelling mechanisms such as cell death, cardiomyocyte hypertrophy, inflammation, fibrosis and metabolism is highlighted. Finally, key challenges and opportunities in circRNA research are discussed, and orientations for future work to address the pharmacological potential of circRNAs in heart failure are proposed.

15.
Pathol Res Pract ; 260: 155402, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38885593

RESUMO

Colorectal cancer (CRC) stands second in terms of mortality and third among the highest prevalent kinds of cancer globally. CRC prevalence is rising in moderately and poorly developed regions and is greater in economically advanced regions. Despite breakthroughs in targeted therapy, resistance to chemotherapeutics remains a significant challenge in the long-term management of CRC. Circular RNAs (circRNAs) have been involved in growing cancer therapy resistance, particularly in CRC, according to an increasing number of studies in recent years. CircRNAs are one of the novel subclasses of non-coding RNAs, previously thought of as viroid. According to studies, circRNAs have been recommended as biological markers for therapeutic targets and diagnostic and prognostic purposes. That is particularly notable given that the expression of circRNAs has been linked to the hallmarks of CRC since they are responsible for drug resistance in CRC patients; thereby, circRNAs are significant for chemotherapy failure. Moreover, knowledge concerning circRNAs remains relatively unclear despite using all these advanced techniques. Here, in this study, we will go over the most recent published work to highlight the critical roles of circRNAs in CRC development and drug resistance and highlight the main strategies to overcome drug resistance to improve clinical outcomes.

16.
Adv Sci (Weinh) ; : e2404822, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38924471

RESUMO

Small extracellular vesicles (sEVs) contain abundant circular RNAs (circRNAs) and are involved in cellular processes, particularly hypoxia. However, the process that packaging of circRNAs into neuronal sEVs under hypoxia is unclear. This study revealed the spatial mechanism of the Fused in Sarcoma protein (FUS) that facilitates the loading of functional circRNAs into sEVs in hypoxia neurons. It is found that FUS translocated from the nucleus to the cytoplasm and is more enriched in hypoxic neuronal sEVs than in normal sEVs. Cytoplasmic FUS formed aggregates with the sEVs marker protein CD63 in cytoplasmic stress granules (SGs) under hypoxic stress. Meanwhile, cytoplasmic FUS recruited of functional cytoplasmic circRNAs to SGs. Upon relief of hypoxic stress and degradation of SGs, cytoplasmic FUS is transported with those circRNAs from SGs to sEVs. Validation of FUS knockout dramatically reduced the recruitment of circRNAs from SGs and led to low circRNA loading in sEVs, which is also confirmed by the accumulation of circRNAs in the cytoplasm. Furthermore, it is showed that the FUS Zf_RanBP domain regulates the transport of circRNAs to sEVs by interacting with hypoxic circRNAs in SGs. Overall, these findings have revealed a FUS-mediated transport mechanism of hypoxia-related cytoplasmic circRNAs loaded into sEVs under hypoxic conditions.

17.
Funct Integr Genomics ; 24(4): 117, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38918231

RESUMO

The role of messenger RNA (mRNA) in biological systems is extremely versatile. However, it's extremely short half-life poses a fundamental restriction on its application. Moreover, the translation efficiency of mRNA is also limited. On the contrary, circular RNAs, also known as circRNAs, are a common and stable form of RNA found in eukaryotic cells. These molecules are synthesized via back-splicing. Both synthetic circRNAs and certain endogenous circRNAs have the potential to encode proteins, hence suggesting the potential of circRNA as a gene expression machinery. Herein, we aim to summarize all engineering aspects that allow exogenous circular RNA (circRNA) to prolong the time that proteins are expressed from full-length RNA signals. This review presents a systematic engineering approach that have been devised to efficiently assemble circRNAs and evaluate several aspects that have an impact on protein production derived from. We have also reviewed how optimization of the key components of circRNAs, including the topology of vector, 5' and 3' untranslated sections, entrance site of the internal ribosome, and engineered aptamers could be efficiently impacting the translation machinery for molecular and metabolic reprogramming. Collectively, molecular and metabolic reprogramming present a novel way of regulating distinctive cellular features, for instance growth traits to neoplastic cells, and offer new possibilities for therapeutic inventions.


Assuntos
RNA Circular , RNA Circular/genética , RNA Circular/metabolismo , Humanos , Animais , Biossíntese de Proteínas , Reprogramação Metabólica
18.
Diabetes Metab Syndr Obes ; 17: 2107-2120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799279

RESUMO

Introduction: Cardiac fibrosis is one of the important causes of heart failure and death in diabetic cardiomyopathy (DCM) patients. Circular RNAs (circRNAs) are covalently closed RNA molecules in eukaryotes and have high stability. Their role in myocardial fibrosis with diabetic cardiomyopathy (DCM) remain to be fully elucidated. This study aimed to understand the expression profiles of circRNAs in myocardial fibrosis with DCM, exploring the possible biomarkers and therapeutic targets for DCM. Methods: At 21 weeks of age, db/db mice established the type 2 DCM model measured by echocardiography, and the cardiac tissue was extracted for Hematoxylin-eosin, Masson's trichrome staining, and transmission electron microscopy. Subsequently, the expression profile of circRNAs in myocardial fibrosis of db/db mice was constructed using microarray hybridization and verified by real-time quantitative polymerase chain reaction. A circRNA-microRNA-messenger RNA coexpression network was constructed, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were done. Results: Compared with normal control mice, db/db mice had 77 upregulated circRNAs and 135 downregulated circRNAs in their chromosomes (fold change ≥1.5, P ≤ 0.05). Moreover, the enrichment analysis of circRNA host genes showed that these differentially expressed circRNAs were mainly involved in mitogen-activated protein kinase signaling pathways. CircPHF20L1, circCLASP1, and circSLC8A1 were the key circRNAs. Moreover, circCLASP1/miR-182-5p/Wnt7a, circSLC8A1/miR-29b-1-5p/Col12a1, and most especially circPHF20L1/miR-29a-3p/Col6a2 might be three novel axes in the development of myocardial fibrosis in DCM. Conclusion: The findings will provide some novel circRNAs and molecular pathways for the prevention or clinical treatment of DCM through intervention with specific circRNAs.

19.
Funct Integr Genomics ; 24(3): 102, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760573

RESUMO

Cardiovascular disease, specifically heart failure (HF), remains a significant concern in the realm of healthcare, necessitating the development of new treatments and biomarkers. The RNA family consists of various subgroups, including microRNAs, PIWI-interacting RNAs (piRAN) and long non-coding RNAs, which have shown potential in advancing personalized healthcare for HF patients. Recent research suggests that circular RNAs, a lesser-known subgroup of RNAs, may offer a novel set of targets and biomarkers for HF. This review will discuss the biogenesis of circular RNAs, their unique characteristics relevant to HF, their role in heart function, and their potential use as biomarkers in the bloodstream. Furthermore, future research directions in this field will be outlined. The stability of exosomal circRNAs makes them suitable as biomarkers, pathogenic regulators, and potential treatments for cardiovascular diseases such as atherosclerosis, acute coronary syndrome, ischemia/reperfusion injury, HF, and peripheral artery disease. Herein, we summarized the role of circular RNAs and their exosomal forms in HF diseases.


Assuntos
Biomarcadores , Exossomos , Insuficiência Cardíaca , RNA Circular , RNA Circular/genética , RNA Circular/metabolismo , Humanos , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Biomarcadores/metabolismo , Exossomos/metabolismo , Exossomos/genética , Animais , MicroRNAs/genética , MicroRNAs/metabolismo
20.
Molecules ; 29(10)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38792263

RESUMO

Oral cancer (OC) is among the most common malignancies in the world. Despite advances in therapy, the worst-case scenario for OC remains metastasis, with a 50% survival rate. Therefore, it is critical to comprehend the pathophysiology of the condition and to create diagnostic and treatment plans for OC. The development of high-throughput genome sequencing has revealed that over 90% of the human genome encodes non-coding transcripts, or transcripts that do not code for any proteins. This paper describes the function of these different kinds of non-coding RNAs (ncRNAs) in OC as well as their intriguing therapeutic potential. The onset and development of OC, as well as treatment resistance, are linked to dysregulated ncRNA expression. These ncRNAs' potentially significant roles in diagnosis and prognosis have been suggested by their differing expression in blood or saliva. We have outlined every promising feature of ncRNAs in the treatment of OC in this study.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais , RNA não Traduzido , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , RNA não Traduzido/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico
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