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MicroRNA-204 Regulates Angiogenesis and Vasculogenic Mimicry in CD44+/CD24− Breast Cancer Stem-like Cells MicroRNA-204 调控 CD44+/CD24- 乳腺癌干样细胞的血管生成和血管生成模拟
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-09 DOI: 10.3390/ncrna10010014
Martha Resendiz-Hernández, Alejandra P. García-Hernández, M. B. Silva-Cázares, Rogelio Coronado-Uribe, Olga N. Hernández-de la Cruz, Lourdes A. Arriaga-Pizano, J. Prieto-Chávez, Yarely M. Salinas-Vera, Eloisa Ibarra-Sierra, Concepción Ortiz-Martínez, C. López-Camarillo
Tumors have high requirements in terms of nutrients and oxygen. Angiogenesis is the classical mechanism for vessel formation. Tumoral vascularization has the function of nourishing the cancer cells to support tumor growth. Vasculogenic mimicry, a novel intratumoral microcirculation system, alludes to the ability of cancer cells to organize in three-dimensional (3D) channel-like architectures. It also supplies the tumors with nutrients and oxygen. Both mechanisms operate in a coordinated way; however, their functions in breast cancer stem-like cells and their regulation by microRNAs remain elusive. In the present study, we investigated the functional role of microRNA-204 (miR-204) on angiogenesis and vasculogenic mimicry in breast cancer stem-like cells. Using flow cytometry assays, we found that 86.1% of MDA-MB-231 and 92% of Hs-578t breast cancer cells showed the CD44+/CD24− immunophenotype representative of cancer stem-like cells (CSCs). The MDA-MB-231 subpopulation of CSCs exhibited the ability to form mammospheres, as expected. Interestingly, we found that the restoration of miR-204 expression in CSCs significantly inhibited the number and size of the mammospheres. Moreover, we found that MDA-MB-231 and Hs-578t CSCs efficiently undergo angiogenesis and hypoxia-induced vasculogenic mimicry in vitro. The transfection of precursor miR-204 in both CSCs was able to impair the angiogenesis in the HUVEC cell model, which was observed as a diminution in the number of polygons and sprouting cells. Remarkably, miR-204 mimics also resulted in the inhibition of vasculogenic mimicry formation in MDA-MB-231 and Hs-578t CSCs, with a significant reduction in the number of channel-like structures and branch points. Mechanistically, the effects of miR-204 were associated with a diminution of pro-angiogenic VEGFA and β-catenin protein levels. In conclusion, our findings indicated that miR-204 abrogates the angiogenesis and vasculogenic mimicry development in breast cancer stem-like cells, suggesting that it could be a potential tool for breast cancer intervention based on microRNA replacement therapies.
肿瘤对营养和氧气的需求很高。血管生成是血管形成的经典机制。肿瘤血管具有滋养癌细胞、支持肿瘤生长的功能。血管生成模拟是一种新型的瘤内微循环系统,暗指癌细胞以三维(3D)通道状结构组织的能力。它还为肿瘤提供营养和氧气。这两种机制以协调的方式运行;然而,它们在乳腺癌干样细胞中的功能及其受 microRNAs 的调控仍难以捉摸。在本研究中,我们研究了microRNA-204(miR-204)对乳腺癌干样细胞血管生成和血管生成模拟的功能作用。通过流式细胞术检测,我们发现86.1%的MDA-MB-231和92%的Hs-578t乳腺癌细胞显示出代表癌症干样细胞(CSCs)的CD44+/CD24-免疫表型。正如预期的那样,MDA-MB-231亚群的癌干细胞具有形成乳球的能力。有趣的是,我们发现恢复 CSCs 中 miR-204 的表达能显著抑制乳腺球的数量和大小。此外,我们还发现 MDA-MB-231 和 Hs-578t CSCs 在体外能有效地进行血管生成和缺氧诱导的血管生成模拟。在 HUVEC 细胞模型中,转染这两种 CSCs 的前体 miR-204 能够损害血管生成,表现为多边形和发芽细胞数量的减少。值得注意的是,miR-204模拟物还能抑制MDA-MB-231和Hs-578t CSCs中血管生成模拟物的形成,通道样结构和分支点的数量显著减少。从机理上讲,miR-204 的作用与促血管生成 VEGFA 和 β-catenin 蛋白水平的降低有关。总之,我们的研究结果表明,miR-204 可抑制乳腺癌干样细胞的血管生成和血管生成模拟发展,这表明它可能是基于微RNA替代疗法干预乳腺癌的一种潜在工具。
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引用次数: 0
MicroRNA-204 Regulates Angiogenesis and Vasculogenic Mimicry in CD44+/CD24− Breast Cancer Stem-like Cells MicroRNA-204 调控 CD44+/CD24- 乳腺癌干样细胞的血管生成和血管生成模拟
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-09 DOI: 10.3390/ncrna10010014
Martha Resendiz-Hernández, Alejandra P. García-Hernández, M. B. Silva-Cázares, Rogelio Coronado-Uribe, Olga N. Hernández-de la Cruz, Lourdes A. Arriaga-Pizano, J. Prieto-Chávez, Yarely M. Salinas-Vera, Eloisa Ibarra-Sierra, Concepción Ortiz-Martínez, C. López-Camarillo
Tumors have high requirements in terms of nutrients and oxygen. Angiogenesis is the classical mechanism for vessel formation. Tumoral vascularization has the function of nourishing the cancer cells to support tumor growth. Vasculogenic mimicry, a novel intratumoral microcirculation system, alludes to the ability of cancer cells to organize in three-dimensional (3D) channel-like architectures. It also supplies the tumors with nutrients and oxygen. Both mechanisms operate in a coordinated way; however, their functions in breast cancer stem-like cells and their regulation by microRNAs remain elusive. In the present study, we investigated the functional role of microRNA-204 (miR-204) on angiogenesis and vasculogenic mimicry in breast cancer stem-like cells. Using flow cytometry assays, we found that 86.1% of MDA-MB-231 and 92% of Hs-578t breast cancer cells showed the CD44+/CD24− immunophenotype representative of cancer stem-like cells (CSCs). The MDA-MB-231 subpopulation of CSCs exhibited the ability to form mammospheres, as expected. Interestingly, we found that the restoration of miR-204 expression in CSCs significantly inhibited the number and size of the mammospheres. Moreover, we found that MDA-MB-231 and Hs-578t CSCs efficiently undergo angiogenesis and hypoxia-induced vasculogenic mimicry in vitro. The transfection of precursor miR-204 in both CSCs was able to impair the angiogenesis in the HUVEC cell model, which was observed as a diminution in the number of polygons and sprouting cells. Remarkably, miR-204 mimics also resulted in the inhibition of vasculogenic mimicry formation in MDA-MB-231 and Hs-578t CSCs, with a significant reduction in the number of channel-like structures and branch points. Mechanistically, the effects of miR-204 were associated with a diminution of pro-angiogenic VEGFA and β-catenin protein levels. In conclusion, our findings indicated that miR-204 abrogates the angiogenesis and vasculogenic mimicry development in breast cancer stem-like cells, suggesting that it could be a potential tool for breast cancer intervention based on microRNA replacement therapies.
肿瘤对营养和氧气的需求很高。血管生成是血管形成的经典机制。肿瘤血管具有滋养癌细胞、支持肿瘤生长的功能。血管生成模拟是一种新型的瘤内微循环系统,暗指癌细胞以三维(3D)通道状结构组织的能力。它还为肿瘤提供营养和氧气。这两种机制以协调的方式运行;然而,它们在乳腺癌干样细胞中的功能及其受 microRNAs 的调控仍难以捉摸。在本研究中,我们研究了microRNA-204(miR-204)对乳腺癌干样细胞血管生成和血管生成模拟的功能作用。通过流式细胞术检测,我们发现86.1%的MDA-MB-231和92%的Hs-578t乳腺癌细胞显示出代表癌症干样细胞(CSCs)的CD44+/CD24-免疫表型。正如预期的那样,MDA-MB-231亚群的癌干细胞具有形成乳球的能力。有趣的是,我们发现恢复 CSCs 中 miR-204 的表达能显著抑制乳腺球的数量和大小。此外,我们还发现 MDA-MB-231 和 Hs-578t CSCs 在体外能有效地进行血管生成和缺氧诱导的血管生成模拟。在 HUVEC 细胞模型中,转染这两种 CSCs 的前体 miR-204 能够损害血管生成,表现为多边形和发芽细胞数量的减少。值得注意的是,miR-204模拟物还能抑制MDA-MB-231和Hs-578t CSCs中血管生成模拟物的形成,通道样结构和分支点的数量显著减少。从机理上讲,miR-204 的作用与促血管生成 VEGFA 和 β-catenin 蛋白水平的降低有关。总之,我们的研究结果表明,miR-204 可抑制乳腺癌干样细胞的血管生成和血管生成模拟发展,这表明它可能是基于微RNA替代疗法干预乳腺癌的一种潜在工具。
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引用次数: 0
The Emerging Role of Non-Coding RNAs (ncRNAs) in Plant Growth, Development, and Stress Response Signaling 非编码 RNA (ncRNA) 在植物生长、发育和应激反应信号传导中的新作用
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-07 DOI: 10.3390/ncrna10010013
Amit Yadav, J. Mathan, Arvind Kumar Dubey, Anuradha Singh
Plant species utilize a variety of regulatory mechanisms to ensure sustainable productivity. Within this intricate framework, numerous non-coding RNAs (ncRNAs) play a crucial regulatory role in plant biology, surpassing the essential functions of RNA molecules as messengers, ribosomal, and transfer RNAs. ncRNAs represent an emerging class of regulators, operating directly in the form of small interfering RNAs (siRNAs), microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). These ncRNAs exert control at various levels, including transcription, post-transcription, translation, and epigenetic. Furthermore, they interact with each other, contributing to a variety of biological processes and mechanisms associated with stress resilience. This review primarily concentrates on the recent advancements in plant ncRNAs, delineating their functions in growth and development across various organs such as root, leaf, seed/endosperm, and seed nutrient development. Additionally, this review broadens its scope by examining the role of ncRNAs in response to environmental stresses such as drought, salt, flood, heat, and cold in plants. This compilation offers updated information and insights to guide the characterization of the potential functions of ncRNAs in plant growth, development, and stress resilience in future research.
植物物种利用各种调控机制来确保可持续的生产力。在这一错综复杂的框架内,大量非编码 RNA(ncRNA)在植物生物学中发挥着至关重要的调控作用,其功能超越了 RNA 分子作为信使、核糖体和转运 RNA 的基本功能。ncRNA 代表了一类新兴的调控因子,直接以小干扰 RNA(siRNA)、microRNA(miRNA)、长非编码 RNA(lnRNA)和环状 RNA(circRNA)的形式发挥作用。这些 ncRNA 在转录、转录后、翻译和表观遗传等不同水平上发挥控制作用。此外,它们还相互影响,促成了与应激复原力相关的各种生物过程和机制。本综述主要集中于植物 ncRNA 的最新进展,阐述了它们在根、叶、种子/胚乳和种子营养发育等不同器官的生长和发育过程中的功能。此外,本综述还研究了 ncRNA 在植物应对干旱、盐分、洪水、高温和严寒等环境胁迫时的作用,从而拓宽了研究范围。这篇综述提供了最新的信息和见解,为今后研究 ncRNA 在植物生长、发育和抗逆性中的潜在功能特性提供了指导。
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引用次数: 0
The Emerging Role of Non-Coding RNAs (ncRNAs) in Plant Growth, Development, and Stress Response Signaling 非编码 RNA (ncRNA) 在植物生长、发育和应激反应信号传导中的新作用
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-07 DOI: 10.3390/ncrna10010013
Amit Yadav, J. Mathan, Arvind Kumar Dubey, Anuradha Singh
Plant species utilize a variety of regulatory mechanisms to ensure sustainable productivity. Within this intricate framework, numerous non-coding RNAs (ncRNAs) play a crucial regulatory role in plant biology, surpassing the essential functions of RNA molecules as messengers, ribosomal, and transfer RNAs. ncRNAs represent an emerging class of regulators, operating directly in the form of small interfering RNAs (siRNAs), microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). These ncRNAs exert control at various levels, including transcription, post-transcription, translation, and epigenetic. Furthermore, they interact with each other, contributing to a variety of biological processes and mechanisms associated with stress resilience. This review primarily concentrates on the recent advancements in plant ncRNAs, delineating their functions in growth and development across various organs such as root, leaf, seed/endosperm, and seed nutrient development. Additionally, this review broadens its scope by examining the role of ncRNAs in response to environmental stresses such as drought, salt, flood, heat, and cold in plants. This compilation offers updated information and insights to guide the characterization of the potential functions of ncRNAs in plant growth, development, and stress resilience in future research.
植物物种利用各种调控机制来确保可持续的生产力。在这一错综复杂的框架内,大量非编码 RNA(ncRNA)在植物生物学中发挥着至关重要的调控作用,其功能超越了 RNA 分子作为信使、核糖体和转运 RNA 的基本功能。ncRNA 代表了一类新兴的调控因子,直接以小干扰 RNA(siRNA)、microRNA(miRNA)、长非编码 RNA(lnRNA)和环状 RNA(circRNA)的形式发挥作用。这些 ncRNA 在转录、转录后、翻译和表观遗传等不同水平上发挥控制作用。此外,它们还相互影响,促成了与应激复原力相关的各种生物过程和机制。本综述主要集中于植物 ncRNA 的最新进展,阐述了它们在根、叶、种子/胚乳和种子营养发育等不同器官的生长和发育过程中的功能。此外,本综述还研究了 ncRNA 在植物应对干旱、盐分、洪水、高温和严寒等环境胁迫时的作用,从而拓宽了研究范围。这篇综述提供了最新的信息和见解,为今后研究 ncRNA 在植物生长、发育和抗逆性中的潜在功能特性提供了指导。
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引用次数: 0
Functional Relevance of Extracellular Vesicle-Derived Long Non-Coding and Circular RNAs in Cancer Angiogenesis 细胞外囊泡衍生的非编码长 RNA 和环状 RNA 在癌症血管生成中的功能相关性
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-06 DOI: 10.3390/ncrna10010012
José A. Peña-Flores, Daniela Muela-Campos, Rebeca Guzmán-Medrano, Diego Enríquez-Espinoza, Karla González-Alvarado
Extracellular vesicles (EVs) are defined as subcellular structures limited by a bilayer lipid membrane that function as important intercellular communication by transporting active biomolecules, such as proteins, amino acids, metabolites, and nucleic acids, including long non-coding RNAs (lncRNAs). These cargos can effectively be delivered to target cells and induce a highly variable response. LncRNAs are functional RNAs composed of at least 200 nucleotides that do not code for proteins. Nowadays, lncRNAs and circRNAs are known to play crucial roles in many biological processes, including a plethora of diseases including cancer. Growing evidence shows an active presence of lnc- and circRNAs in EVs, generating downstream responses that ultimately affect cancer progression by many mechanisms, including angiogenesis. Moreover, many studies have revealed that some tumor cells promote angiogenesis by secreting EVs, which endothelial cells can take up to induce new vessel formation. In this review, we aim to summarize the bioactive roles of EVs with lnc- and circRNAs as cargo and their effect on cancer angiogenesis. Also, we discuss future clinical strategies for cancer treatment based on current knowledge of circ- and lncRNA-EVs.
细胞外囊泡(EVs)被定义为受双层脂膜限制的亚细胞结构,通过运输活性生物大分子,如蛋白质、氨基酸、代谢物和核酸,包括长非编码 RNAs(lncRNAs),发挥重要的细胞间通讯功能。这些载体可以有效地输送到靶细胞,并诱发高度可变的反应。LncRNA 是由至少 200 个核苷酸组成的功能性 RNA,不编码蛋白质。如今,lncRNAs 和 circRNAs 在许多生物过程(包括癌症等多种疾病)中发挥着至关重要的作用。越来越多的证据表明,lncRNA 和 circRNA 在 EVs 中活跃存在,产生下游反应,最终通过多种机制(包括血管生成)影响癌症的进展。此外,许多研究发现,一些肿瘤细胞通过分泌 EVs 促进血管生成,而内皮细胞可以吸收这些 EVs 诱导新血管的形成。在这篇综述中,我们旨在总结以 lnc- 和 circRNAs 为载体的 EVs 的生物活性作用及其对癌症血管生成的影响。此外,我们还将根据目前对circRNA和lncRNA-EVs的了解,讨论未来癌症治疗的临床策略。
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引用次数: 0
Functional Relevance of Extracellular Vesicle-Derived Long Non-Coding and Circular RNAs in Cancer Angiogenesis 细胞外囊泡衍生的非编码长 RNA 和环状 RNA 在癌症血管生成中的功能相关性
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-06 DOI: 10.3390/ncrna10010012
José A. Peña-Flores, Daniela Muela-Campos, Rebeca Guzmán-Medrano, Diego Enríquez-Espinoza, Karla González-Alvarado
Extracellular vesicles (EVs) are defined as subcellular structures limited by a bilayer lipid membrane that function as important intercellular communication by transporting active biomolecules, such as proteins, amino acids, metabolites, and nucleic acids, including long non-coding RNAs (lncRNAs). These cargos can effectively be delivered to target cells and induce a highly variable response. LncRNAs are functional RNAs composed of at least 200 nucleotides that do not code for proteins. Nowadays, lncRNAs and circRNAs are known to play crucial roles in many biological processes, including a plethora of diseases including cancer. Growing evidence shows an active presence of lnc- and circRNAs in EVs, generating downstream responses that ultimately affect cancer progression by many mechanisms, including angiogenesis. Moreover, many studies have revealed that some tumor cells promote angiogenesis by secreting EVs, which endothelial cells can take up to induce new vessel formation. In this review, we aim to summarize the bioactive roles of EVs with lnc- and circRNAs as cargo and their effect on cancer angiogenesis. Also, we discuss future clinical strategies for cancer treatment based on current knowledge of circ- and lncRNA-EVs.
细胞外囊泡(EVs)被定义为受双层脂膜限制的亚细胞结构,通过运输活性生物大分子,如蛋白质、氨基酸、代谢物和核酸,包括长非编码 RNAs(lncRNAs),发挥重要的细胞间通讯功能。这些载体可以有效地输送到靶细胞,并诱发高度可变的反应。LncRNA 是由至少 200 个核苷酸组成的功能性 RNA,不编码蛋白质。如今,lncRNAs 和 circRNAs 在许多生物过程(包括癌症等多种疾病)中发挥着至关重要的作用。越来越多的证据表明,lncRNA 和 circRNA 在 EVs 中活跃存在,产生下游反应,最终通过多种机制(包括血管生成)影响癌症的进展。此外,许多研究发现,一些肿瘤细胞通过分泌 EVs 促进血管生成,而内皮细胞可以吸收这些 EVs 诱导新血管的形成。在这篇综述中,我们旨在总结以 lnc- 和 circRNAs 为载体的 EVs 的生物活性作用及其对癌症血管生成的影响。此外,我们还将根据目前对circRNA和lncRNA-EVs的了解,讨论未来癌症治疗的临床策略。
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引用次数: 0
Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD 与 MAFLD 发病有关的环状 RNA、非编码 RNA 和 N6-甲基腺苷
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-05 DOI: 10.3390/ncrna10010011
Moeka Nakashima, Naoko Suga, Yuka Ikeda, Sayuri Yoshikawa, Satoru Matsuda
Noncoding RNAs (ncRNAs), including circular RNAs (circRNAs) and N6-methyladenosine (m6A), have been shown to play a critical role in the development of various diseases including obesity and metabolic disorder-associated fatty liver disease (MAFLD). Obesity is a chronic disease caused by excessive fat accumulation in the body, which has recently become more prevalent and is the foremost risk factor for MAFLD. Causes of obesity may involve the interaction of genetic, behavioral, and social factors. m6A RNA methylation might add a novel inspiration for understanding the development of obesity and MAFLD with post-transcriptional regulation of gene expression. In particular, circRNAs, microRNAs (miRNAs), and m6A might be implicated in the progression of MAFLD. Interestingly, m6A modification can modulate the translation, degradation, and other functions of ncRNAs. miRNAs/circRNAs can also modulate m6A modifications by affecting writers, erasers, and readers. In turn, ncRNAs could modulate the expression of m6A regulators in different ways. However, there is limited evidence on how these ncRNAs and m6A interact to affect the promotion of liver diseases. It seems that m6A can occur in DNA, RNA, and proteins that may be associated with several biological properties. This study provides a mechanistic understanding of the association of m6A modification and ncRNAs with liver diseases, especially for MAFLD. Comprehension of the association between m6A modification and ncRNAs may contribute to the development of treatment tactics for MAFLD.
非编码 RNA(ncRNA),包括环状 RNA(circRNA)和 N6-甲基腺苷(m6A),已被证明在包括肥胖症和代谢紊乱相关性脂肪肝(MAFLD)在内的各种疾病的发病过程中发挥着关键作用。肥胖症是一种由体内脂肪过度堆积引起的慢性疾病,近来变得越来越普遍,也是 MAFLD 的首要风险因素。肥胖的原因可能涉及遗传、行为和社会因素的相互作用。m6A RNA 甲基化可能为了解肥胖和 MAFLD 的发展提供一个新的灵感,即基因表达的转录后调控。特别是,circRNAs、microRNAs (miRNAs) 和 m6A 可能与 MAFLD 的进展有关。有趣的是,m6A 的修饰可以调节 ncRNAs 的翻译、降解和其他功能。miRNAs/circRNAs 还可以通过影响书写者、擦除者和阅读者来调节 m6A 的修饰。反过来,ncRNA 也能以不同方式调节 m6A 调节因子的表达。然而,关于这些 ncRNA 与 m6A 如何相互作用以影响肝病的发生,目前的证据还很有限。看来,m6A 可出现在 DNA、RNA 和蛋白质中,可能与多种生物特性有关。这项研究从机理上揭示了 m6A 修饰和 ncRNA 与肝病(尤其是 MAFLD)的关系。了解 m6A 修饰与 ncRNA 之间的关联可能有助于制定 MAFLD 的治疗策略。
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引用次数: 0
Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD 与 MAFLD 发病有关的环状 RNA、非编码 RNA 和 N6-甲基腺苷
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-05 DOI: 10.3390/ncrna10010011
Moeka Nakashima, Naoko Suga, Yuka Ikeda, Sayuri Yoshikawa, Satoru Matsuda
Noncoding RNAs (ncRNAs), including circular RNAs (circRNAs) and N6-methyladenosine (m6A), have been shown to play a critical role in the development of various diseases including obesity and metabolic disorder-associated fatty liver disease (MAFLD). Obesity is a chronic disease caused by excessive fat accumulation in the body, which has recently become more prevalent and is the foremost risk factor for MAFLD. Causes of obesity may involve the interaction of genetic, behavioral, and social factors. m6A RNA methylation might add a novel inspiration for understanding the development of obesity and MAFLD with post-transcriptional regulation of gene expression. In particular, circRNAs, microRNAs (miRNAs), and m6A might be implicated in the progression of MAFLD. Interestingly, m6A modification can modulate the translation, degradation, and other functions of ncRNAs. miRNAs/circRNAs can also modulate m6A modifications by affecting writers, erasers, and readers. In turn, ncRNAs could modulate the expression of m6A regulators in different ways. However, there is limited evidence on how these ncRNAs and m6A interact to affect the promotion of liver diseases. It seems that m6A can occur in DNA, RNA, and proteins that may be associated with several biological properties. This study provides a mechanistic understanding of the association of m6A modification and ncRNAs with liver diseases, especially for MAFLD. Comprehension of the association between m6A modification and ncRNAs may contribute to the development of treatment tactics for MAFLD.
非编码 RNA(ncRNA),包括环状 RNA(circRNA)和 N6-甲基腺苷(m6A),已被证明在包括肥胖症和代谢紊乱相关性脂肪肝(MAFLD)在内的各种疾病的发病过程中发挥着关键作用。肥胖症是一种由体内脂肪过度堆积引起的慢性疾病,近来变得越来越普遍,也是 MAFLD 的首要风险因素。肥胖的原因可能涉及遗传、行为和社会因素的相互作用。m6A RNA 甲基化可能为了解肥胖和 MAFLD 的发展提供一个新的灵感,即基因表达的转录后调控。特别是,circRNAs、microRNAs (miRNAs) 和 m6A 可能与 MAFLD 的进展有关。有趣的是,m6A 的修饰可以调节 ncRNAs 的翻译、降解和其他功能。miRNAs/circRNAs 还可以通过影响书写者、擦除者和阅读者来调节 m6A 的修饰。反过来,ncRNA 也能以不同方式调节 m6A 调节因子的表达。然而,关于这些 ncRNA 与 m6A 如何相互作用以影响肝病的发生,目前的证据还很有限。看来,m6A 可出现在 DNA、RNA 和蛋白质中,可能与多种生物特性有关。这项研究从机理上揭示了 m6A 修饰和 ncRNA 与肝病(尤其是 MAFLD)的关系。了解 m6A 修饰与 ncRNA 之间的关联可能有助于制定 MAFLD 的治疗策略。
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引用次数: 0
Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease. 研究非编码 RNA 在非酒精性脂肪肝中的作用
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-31 DOI: 10.3390/ncrna10010010
Samar A Zailaie, Basmah B Khoja, Jumana J Siddiqui, Mohammad H Mawardi, Emily Heaphy, Amjad Aljagthmi, Consolato M Sergi

Non-coding RNAs (ncRNAs) are RNA molecules that do not code for protein but play key roles in regulating cellular processes. NcRNAs globally affect gene expression in diverse physiological and pathological contexts. Functionally important ncRNAs act in chromatin modifications, in mRNA stabilization and translation, and in regulation of various signaling pathways. Non-alcoholic fatty liver disease (NAFLD) is a set of conditions caused by the accumulation of triacylglycerol in the liver. Studies of ncRNA in NAFLD are limited but have demonstrated that ncRNAs play a critical role in the pathogenesis of NAFLD. In this review, we summarize NAFLD's pathogenesis and clinical features, discuss current treatment options, and review the involvement of ncRNAs as regulatory molecules in NAFLD and its progression to non-alcoholic steatohepatitis (NASH). In addition, we highlight signaling pathways dysregulated in NAFLD and review their crosstalk with ncRNAs. Having a thorough understanding of the disease process's molecular mechanisms will facilitate development of highly effective diagnostic and therapeutic treatments. Such insights can also inform preventive strategies to minimize the disease's future development.

非编码 RNA(ncRNA)是不编码蛋白质的 RNA 分子,但在调节细胞过程中发挥着关键作用。在不同的生理和病理环境中,NcRNA 会全面影响基因表达。功能重要的 ncRNA 在染色质修饰、mRNA 稳定和翻译以及各种信号通路的调控中发挥作用。非酒精性脂肪肝(NAFLD)是由三酰甘油在肝脏中蓄积引起的一系列疾病。对非酒精性脂肪肝中 ncRNA 的研究有限,但已证明 ncRNA 在非酒精性脂肪肝的发病机制中起着关键作用。在这篇综述中,我们总结了非酒精性脂肪肝的发病机制和临床特征,讨论了当前的治疗方案,并回顾了 ncRNA 作为调控分子参与非酒精性脂肪肝及其向非酒精性脂肪性肝炎(NASH)发展的过程。此外,我们还强调了非酒精性脂肪肝中失调的信号通路,并回顾了它们与 ncRNA 的相互影响。透彻了解疾病过程的分子机制将有助于开发高效的诊断和治疗方法。这些见解还可以为预防策略提供依据,从而最大限度地减少疾病的未来发展。
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引用次数: 0
HGSMDA: miRNA-Disease Association Prediction Based on HyperGCN and Sørensen-Dice Loss. HGSMDA:基于 HyperGCN 和 Sørensen-Dice Loss 的 miRNA-疾病关联预测。
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-26 DOI: 10.3390/ncrna10010009
Zhenghua Chang, Rong Zhu, Jinxing Liu, Junliang Shang, Lingyun Dai

Biological research has demonstrated the significance of identifying miRNA-disease associations in the context of disease prevention, diagnosis, and treatment. However, the utilization of experimental approaches involving biological subjects to infer these associations is both costly and inefficient. Consequently, there is a pressing need to devise novel approaches that offer enhanced accuracy and effectiveness. Presently, the predominant methods employed for predicting disease associations rely on Graph Convolutional Network (GCN) techniques. However, the Graph Convolutional Network algorithm, which is locally aggregated, solely incorporates information from the immediate neighboring nodes of a given node at each layer. Consequently, GCN cannot simultaneously aggregate information from multiple nodes. This constraint significantly impacts the predictive efficacy of the model. To tackle this problem, we propose a novel approach, based on HyperGCN and Sørensen-Dice loss (HGSMDA), for predicting associations between miRNAs and diseases. In the initial phase, we developed multiple networks to represent the similarity between miRNAs and diseases and employed GCNs to extract information from diverse perspectives. Subsequently, we draw into HyperGCN to construct a miRNA-disease heteromorphic hypergraph using hypernodes and train GCN on the graph to aggregate information. Finally, we utilized the Sørensen-Dice loss function to evaluate the degree of similarity between the predicted outcomes and the ground truth values, thereby enabling the prediction of associations between miRNAs and diseases. In order to assess the soundness of our methodology, an extensive series of experiments was conducted employing the Human MicroRNA Disease Database (HMDD v3.2) as the dataset. The experimental outcomes unequivocally indicate that HGSMDA exhibits remarkable efficacy when compared to alternative methodologies. Furthermore, the predictive capacity of HGSMDA was corroborated through a case study focused on colon cancer. These findings strongly imply that HGSMDA represents a dependable and valid framework, thereby offering a novel avenue for investigating the intricate association between miRNAs and diseases.

生物学研究表明,确定 miRNA 与疾病的关联对于疾病的预防、诊断和治疗具有重要意义。然而,利用涉及生物实验对象的实验方法来推断这些关联既昂贵又低效。因此,迫切需要设计出能提高准确性和有效性的新型方法。目前,预测疾病关联的主要方法依赖于图卷积网络(GCN)技术。然而,图卷积网络算法是局部聚合的,每层只包含给定节点的近邻节点的信息。因此,GCN 无法同时聚合来自多个节点的信息。这一限制极大地影响了模型的预测效果。为了解决这个问题,我们提出了一种基于 HyperGCN 和 Sørensen-Dice loss(HGSMDA)的新方法,用于预测 miRNA 与疾病之间的关联。在初始阶段,我们开发了多个网络来表示 miRNA 与疾病之间的相似性,并利用 GCN 从不同角度提取信息。随后,我们借鉴 HyperGCN,利用超节点构建了 miRNA-疾病异构超图,并在图上训练 GCN 以汇总信息。最后,我们利用 Sørensen-Dice 损失函数来评估预测结果与基本真实值之间的相似程度,从而预测 miRNA 与疾病之间的关联。为了评估我们方法的合理性,我们以人类微小核糖核酸疾病数据库(HMDD v3.2)为数据集,进行了一系列广泛的实验。实验结果明确表明,与其他方法相比,HGSMDA 具有显著的功效。此外,一项以结肠癌为重点的案例研究也证实了 HGSMDA 的预测能力。这些发现有力地表明,HGSMDA 是一个可靠、有效的框架,从而为研究 miRNA 与疾病之间错综复杂的联系提供了一条新途径。
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Non-Coding RNA
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