scholarly journals MicroRNAs’ Involvement in Osteoarthritis and the Prospects for Treatments

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Xiao-Ming Yu ◽  
Hao-Ye Meng ◽  
Xue-Ling Yuan ◽  
Yu Wang ◽  
Quan-Yi Guo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Genetic Changes ◽  
Future Studies ◽  
Small Noncoding Rnas ◽  
Cartilage Homeostasis ◽  
Target Binding ◽  
And Cartilage

Osteoarthritis (OA) is a chronic disease and its etiology is complex. With increasing OA incidence, more and more people are facing heavy financial and social burdens from the disease. Genetics-related aspects of OA pathogenesis are not well understood. Recent reports have examined the molecular mechanisms and genes related to OA. It has been realized that genetic changes in articular cartilage and bone may contribute to OA’s development. Osteoclasts, osteoblasts, osteocytes, and chondrocytes in joints must express appropriate genes to achieve tissue homeostasis, and errors in this can cause OA. MicroRNAs (miRNAs) are small noncoding RNAs that have been discovered to be overarching regulators of gene expression. Their ability to repress many target genes and their target-binding specificity indicate a complex network of interactions, which is still being defined. Many studies have focused on the role of miRNAs in bone and cartilage and have identified numbers of miRNAs that play important roles in regulating bone and cartilage homeostasis. Those miRNAs may also be involved in the pathology of OA, which is the focus of this review. Future studies on the role of miRNAs in OA will provide important clues leading to a better understanding of the mechanism(s) of OA and, more particularly, to the development of therapeutic targets for OA.

scholarly journals Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

2021 ◽  
Vol 22 (11) ◽  
pp. 5711
Author(s):  
Julian Zacharjasz ◽  
Anna M. Mleczko ◽  
Paweł Bąkowski ◽  
Tomasz Piontek ◽  
Kamilla Bąkowska-Żywicka
Keyword(s):  
Knee Osteoarthritis ◽  
Noncoding Rnas ◽  
Pathological Process ◽  
Joint Disease ◽  
Limited Information ◽  
Genetic Changes ◽  
Small Noncoding Rnas ◽  
Knee Oa ◽  
Cartilage Homeostasis

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.

scholarly journals Looking for Pyroptosis-Modulating miRNAs as a Therapeutic Target for Improving Myocardium Survival

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Seahyoung Lee ◽  
Eunhyun Choi ◽  
Min-Ji Cha ◽  
Ki-Chul Hwang
Keyword(s):  
Cell Death ◽  
Cardiovascular Diseases ◽  
Inflammatory Response ◽  
Therapeutic Target ◽  
Noncoding Rnas ◽  
Future Studies ◽  
Small Noncoding Rnas ◽  
Regulated Cell Death ◽  
A Current

Pyroptosis is the most recently identified type of regulated cell death with inflammatory response and has characteristics distinct from those of apoptosis or necrosis. Recently, independent studies have reported that small noncoding RNAs termed microRNAs (miRNAs) are involved in the regulation of pyroptosis. Nevertheless, only a handful of empirical data regarding miRNA-dependent regulation of pyroptosis is currently available. This review is aimed to provide a current update on the role of miRNAs in pyroptosis and to offer suggestions for future studies probing miRNAs as a linker connecting pyroptosis to various cardiovascular diseases (CVDs) and their potential as a therapeutic target for preventing excessive cell death of myocardium during CVDs.

scholarly journals miR-30 Family: A Promising Regulator in Development and Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ling Mao ◽  
Shiming Liu ◽  
Lin Hu ◽  
Li Jia ◽  
Hairong Wang ◽  
...  
Keyword(s):  
Target Genes ◽  
Noncoding Rnas ◽  
Small Noncoding Rnas ◽  
Related Disease ◽  
The Future

MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate posttranscriptional expression of target genes. Accumulating evidences have demonstrated that the miR-30 family, as a member of microRNAs, played a crucial regulating role in the development of tissues and organs and the pathogenesis of clinical diseases, which indicated that it may be a promising regulator in development and disease. This review aims to clarify the current progress on the regulating role of miR-30 family in tissues and organs development and related disease and highlight their research prospective in the future.

scholarly journals Epi-miRNAs: Regulators of the Histone Modification Machinery in Human Cancer

2022 ◽  
Vol 2022 ◽  
pp. 1-22
Author(s):  
Deniz Mortazavi ◽  
Behnoush Sohrabi ◽  
Meysam Mosallaei ◽  
Ziba Nariman-Saleh-Fam ◽  
Milad Bastami ◽  
...  
Keyword(s):  
Histone Modification ◽  
Cell Fate ◽  
Target Genes ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Fine Tuning ◽  
Small Noncoding Rnas ◽  
Histone Modifiers ◽  
Histone Modifying Enzymes

Cancer is a leading cause of death and disability worldwide. Epigenetic deregulation is one of the most critical mechanisms in carcinogenesis and can be classified into effects on DNA methylation and histone modification. MicroRNAs are small noncoding RNAs involved in fine-tuning their target genes after transcription. Various microRNAs control the expression of histone modifiers and are involved in a variety of cancers. Therefore, overexpression or downregulation of microRNAs can alter cell fate and cause malignancies. In this review, we discuss the role of microRNAs in regulating the histone modification machinery in various cancers, with a focus on the histone-modifying enzymes such as acetylases, deacetylases, methyltransferases, demethylases, kinases, phosphatases, desumoylases, ubiquitinases, and deubiquitinases. Understanding of microRNA-related aberrations underlying histone modifiers in pathogenesis of different cancers can help identify novel therapeutic targets or early detection approaches that allow better management of patients or monitoring of treatment response.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

scholarly journals The role of m6A modification in the biological functions and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiulin Jiang ◽  
Baiyang Liu ◽  
Zhi Nie ◽  
Lincan Duan ◽  
Qiuxia Xiong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Rna Modification ◽  
Biological Functions ◽  
Rna Methylation ◽  
Downstream Target ◽  
Different Types ◽  
M6a Rna Methylation

AbstractN6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

scholarly journals Mitochondrial microRNAs: A Putative Role in Tissue Regeneration

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 486
Author(s):  
Sílvia C. Rodrigues ◽  
Renato M. S. Cardoso ◽  
Filipe V. Duarte
Keyword(s):  
Tissue Regeneration ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Noncoding Rnas ◽  
Atp Synthesis ◽  
Mitochondrial Proteins ◽  
Cellular Mechanisms ◽  
Small Noncoding Rnas ◽  
Mitochondrial Ribosome

The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment.

scholarly journals Discovery of MicroRNAs and Their Target Genes Related to Drought in Paulownia “Yuza 1” by High-Throughput Sequencing

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Minjie Deng ◽  
Yabing Cao ◽  
Zhenli Zhao ◽  
Lu Yang ◽  
Yanfang Zhang ◽  
...  
Keyword(s):  
Drought Stress ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Plant Hormone ◽  
Target Genes ◽  
Reference Data ◽  
Relevant Information ◽  
Putative Target

Understanding the role of miRNAs in regulating the molecular mechanisms responsive to drought stress was studied in Paulownia “yuza 1.” Two small RNA libraries and two degradome libraries were, respectively, constructed and sequenced in order to detect miRNAs and their target genes associated with drought stress. A total of 107 miRNAs and 42 putative target genes were identified in this study. Among them, 77 miRNAs were differentially expressed between drought-treated Paulownia “yuza 1” and the control (60 downregulated and 17 upregulated). The predicted target genes were annotated using the GO, KEGG, and Nr databases. According to the functional classification of the target genes, Paulownia “yuza 1” may respond to drought stress via plant hormone signal transduction, photosynthesis, and osmotic adjustment. Furthermore, the expression levels of seven miRNAs (ptf-miR157b, ptf-miR159b, ptf-miR398a, ptf-miR9726a, ptf-M2153, ptf-M2218, and ptf-M24a) and their corresponding target genes were validated by quantitative real-time PCR. The results provide relevant information for understanding the molecular mechanism of Paulownia resistance to drought and reference data for researching drought resistance of other trees.

scholarly journals Coilin enhances phosphorylation and stability of DGCR8 and promotes miRNA biogenesis

2021 ◽  
pp. mbc.E21-05-0225
Author(s):  
Katheryn E. Lett ◽  
Madelyn K. Logan ◽  
Douglas M. McLaurin ◽  
Michael D. Hebert
Keyword(s):  
Noncoding Rnas ◽  
Mature Mirnas ◽  
Cajal Body ◽  
Mirna Biogenesis ◽  
Regulatory Interaction ◽  
Small Noncoding Rnas ◽  
Control Gene Expression ◽  
Processing Steps ◽  
Posttranscriptional Level

MicroRNAs (miRNAs) are ∼22 nt small noncoding RNAs that control gene expression at the posttranscriptional level through translational inhibition and destabilization of their target mRNAs. The biogenesis of miRNAs involves a series of processing steps beginning with cropping of the primary miRNA transcript by the Microprocessor complex, which is comprised of Drosha and DGCR8. Here we report a novel regulatory interaction between the Microprocessor components and coilin, the Cajal Body (CB) marker protein. Coilin knockdown causes alterations in the level of primary and mature miRNAs, let-7a and miR-34a, and their miRNA targets, HMGA2 and Notch1, respectively. We also found that coilin knockdown affects the levels of DGCR8 and Drosha in cells with (HeLa) and without (WI-38) CBs. To further explore the role of coilin in miRNA biogenesis, we conducted a series of co-immunoprecipitation experiments using coilin and DGCR8 constructs, which revealed that coilin and DGCR8 can form a complex. Additionally, our results indicate that phosphorylation of DGCR8, which has been shown to increase protein stability, is impacted by coilin knockdown. Collectively, our results implicate coilin as a member of the regulatory network governing miRNA biogenesis.

Abstract W MP86: Microrna-146a Modulates Neurogenesis And Oligodendrogenesis After Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Xianshuang Liu ◽  
Chopp Michael ◽  
Xinli Wang ◽  
Li Zhang ◽  
Yisheng Cui ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Target Genes ◽  
Artery Occlusion ◽  
Locked Nucleic Acid ◽  
Myelin Proteins ◽  
Oligodendrocyte Progenitor Cells ◽  
Marker Proteins

Background: Neurogenesis and oligodendrogenesis are associated with functional recovery after stroke. However, the molecules that regulate the generation of new neurons and oligodendrocytes have not been fully investigated. MicroRNAs (miRNAs) post-transcriptionally regulate gene expression. MiR-146a has been reported to regulate the immune response in cells, but the role of miR-146a in neural (NPCs) and oligodendrocyte progenitor cells (OPCs) remains unexplored. Methods and Results: Adult Wistar rats were subjected to right middle cerebral artery occlusion (MCAo). In situ hybridization using locked nucleic acid (LNA)probes against miR-146a showed that stroke considerably increased miR-146a density in the subventricular zone (SVZ, 19 ± 1 vs 6 ± 0.1 area/mm2 in non-MCAo group, p<0.05, n=4/group) and corpus callosum (24 ± 3 vs 8±1 area/mm2 in non-MCAo group) of the ischemic hemisphere. Quantitative RT-PCR also demonstrated a marked upregulation of miR-146a transcript in ischemic NPCs (8.5 fold), suggesting an important role in stroke-induced neurogenesis and oligodendrogenesis. To test its biological function, we over-expressed miR-146a in neural progenitor cells by transfection of miR-146a mimics using nucleofector and found that elevation of miR-146a significantly increased the percentage of Tuj1+ neuroblasts (5 ± 0.3 vs 1 ± 0.2%, p<0.05, n=6/group) and O4+ OPCs (10 ± 1 vs 4 ± 0.4%, p<0.05). Moreover, over-expression of miR-146a in primary cultured OPCs significantly increased several myelin proteins including MBP and PLP, and decreased levels of OPC marker proteins including PDGFRα and NG2, whereas attenuation of miR-146a by siRNA against miR-146a suppressed myelin proteins and augmented OPC marker proteins. Furthermore, miR-146a levels in the OPCs were inversely related to IRAK1 proteins, one of miR-146a target genes. Attenuation of IRAK1 in OPCs substantially increased myelin proteins, indicating that miR-146a mediates oligodendrocyte maturation via targeting IRAK1. Conclusion: Our data provide new insight into molecular mechanisms underlying stroke-induced neurogenesis and oligodendrogenesis by revealing a novel role of miR-146a in NPCs and OPCs, which has potential to be used as a new therapy for neurorecovery after stroke.

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