MiR-490-3p inhibits osteogenic differentiation in thoracic ligamentum flavum cells by targeting FOXO1

Yang, Xiaoxi; Qu, Xiaochen; Meng, Xiangyu; Li, Mengtao; Fan, Dongwei; Fan, Tianqi; Huang, Ann; Chen, Zhongqiang; Zhang, Chi

doi:10.7150/ijbs.26686

Cited by 18 publications

(22 citation statements)

References 39 publications

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“…MiR-490-3p Yang et al (2018b) first investigated the function of miR-490-3p in TOLF. MiR-490-3p presented downregulated expression during OLF process, and its overexpression further depressed osteogenic differentiation of ligament fibroblasts.…”

Section: Mir-615-3pmentioning

confidence: 99%

Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions

et al. 2021

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Pathological changes in the ligamentum flavum (LF) can be defined as a process of chronic progressive aberrations in the nature and structure of ligamentous tissues characterized by increased thickness, reduced elasticity, local calcification, or aggravated ossification, which may cause severe myelopathy, radiculopathy, or both. Hypertrophy of ligamentum flavum (HLF) and ossification of ligamentum flavum (OLF) are clinically common entities. Though accumulated evidence has indicated both genetic and environmental factors could contribute to the initiation and progression of HLF/OLF, the definite pathogenesis remains fully unclear. MicroRNAs (miRNAs), one of the important epigenetic modifications, are short single-stranded RNA molecules that regulate protein-coding gene expression at posttranscriptional level, which can disclose the mechanism underlying diseases, identify valuable biomarkers, and explore potential therapeutic targets. Considering that miRNAs play a central role in regulating gene expression, we summarized current studies from the point of view of miRNA-related molecular regulation networks in HLF/OLF. Exploratory studies revealed a variety of miRNA expression profiles and identified a battery of upregulated and downregulated miRNAs in OLF/HLF patients through microarray datasets or transcriptome sequencing. Experimental studies validated the roles of specific miRNAs (e.g., miR-132-3p, miR-199b-5p in OLF, miR-155, and miR-21 in HLF) in regulating fibrosis or osteogenesis differentiation of LF cells and related target genes or molecular signaling pathways. Finally, we discussed the perspectives and challenges of miRNA-based molecular mechanism, diagnostic biomarkers, and therapeutic targets of HLF/OLF.

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Section: Mir-615-3pmentioning

confidence: 99%

Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions

et al. 2021

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“…Importantly, miR‐490 expression has also been correlated to the disease progression other than cancer (Table 2). Low miR‐490 levels were reported in atherosclerosis (Liu et al, 2019; Sun et al, 2013), chondrogenesis (Zhang et al, 2012), delayed‐type hypersensitivity (Singh et al, 2016), depression (Svenningsen et al, 2016), embryonic development (B. Xu et al, 2015), ischemia–reperfusion injury (heart; Wu et al, 2020), kidney toxicity (Marin et al, 2019), thoracic ossification of ligamentum flavum (TOLF; Yang et al, 2018) and tuberous sclerosis complex (Cai et al, 2017). Also, upregulated expression of miR‐490 was shown in coronary disease (Freedman et al, 2012), development (Xu et al, 2013), essential thrombocythemia (Tran et al, 2020), ulcerative colitis (Huang et al, 2017), dyslipidemia (Lim et al, 2016) and focal segmental glomerulosclerosis (Zhang et al, 2014).…”

Section: Status Of Mir‐490 In Other Diseasesmentioning

confidence: 99%

“…Low miR-490 levels were reported in atherosclerosis (Liu et al, 2019;Sun et al, 2013), chondrogenesis (Zhang et al, 2012), delayed-type hypersensitivity (Singh et al, 2016), depression (Svenningsen et al, 2016), embryonic development (B. , ischemia-reperfusion injury (heart; Wu et al, 2020), kidney toxicity (Marin et al, 2019), thoracic ossification of ligamentum flavum (TOLF; Yang et al, 2018) and tuberous sclerosis complex (Cai et al, 2017). Also, upregulated expression of miR-490 was shown in coronary disease (Freedman et al, 2012), development (Xu et al, 2013), essential thrombocythemia (Tran et al, 2020), ulcerative colitis (Huang et al, 2017), dyslipidemia (Lim et al, 2016) Overall, miR-490 was shown to possess a protective function in various diseases (Liu et al, 2019;Sun et al, 2013;Yang et al, 2018) whereas it was shown to promote the disease phenotype in irritable bowel syndrome and ischemia-reperfusion injury (heart; Ren et al, 2017;Wu et al, 2020). However, functional characterization of miR-490 is relatively less explored in the majority of the disease models and needs further evaluation.…”

Section: Status Of Mir-490 In Other Diseasesmentioning

confidence: 99%

miR‐490: A potential biomarker and therapeutic target in cancer and other diseases

Vinchure

Kulshreshtha

2020

Journal Cellular Physiology

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MicroRNAs (miRNAs) are small non‐coding RNAs that function as posttranscriptional gene regulators. Among a pool of >2600 known human mature miRNAs, only a small subset have been functionally interrogated and a further smaller pool shown to be associated with the pathogenesis of a variety of diseases suggesting their critical role in maintaining homeostasis. Here, we draw your attention to one such miRNA, miR‐490, that has been reported to be deregulated in a myriad of diseases (23 diseases) ranging from cardiomyopathy, depression, and developmental disorders to many cancer types (28 cancer types), such as hepatocellular carcinoma, gastric cancer, cancers of the reproductive and central nervous system among others. The prognostic and diagnostic potential of miR‐490 has been reported in many diseases including cancer underlining its clinical relevance. We also collate a complex plethora of epigenetic (histone and DNA methylation), transcriptional (TF), and posttranscriptional (lncRNA and circRNA) mechanisms that have been shown to tightly regulate miR‐490 levels. The targets of miR‐490 involve a range of cancer‐related genes involved in the regulation of various cancer hallmarks like cell proliferation, migration, and invasion, apoptotic cell death, angiogenesis, and so forth. Overall, our in‐depth review highlights for the first time the emerging role of miR‐490 in disease pathology, diagnosis, and prognosis that assigns a unique therapeutic potential to miR‐490 in the era of precision medicine.

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“…It is generally believed that genetic and environmental factors can contribute to the occurrence and development of OLF. 7 However, its definite pathomechanism remains inadequately understood. Histologically, its pathological nature is considered as endochondral osteogenesis involving the differentiation of ligament fibroblasts into osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

Integrating Bioinformatic Strategies with Real-World Data to Infer Distinctive Immunocyte Infiltration Landscape and Immunologically Relevant Transcriptome Fingerprints in Ossification of Ligamentum Flavum

Zhang

Chen

et al. 2021

JIR

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Purpose Ossification of the ligamentum flavum (OLF) is a multifactorial disease characterized by an insidious and debilitating process of abnormal bone formation in ligamentum tissues. However, its definite pathogenesis has not been fully elucidated. Potential links between the immune system and various forms of heterotopic ossification have been discussed for many years, whereas no research investigated the immune effects on the initiation and development of OLF. Therefore, we attempt to shed light on this issue. Methods A series of bioinformatic algorithms were integrated to evaluate the immune score and the immunocyte infiltration patterns between OLF and normal samples, screen OLF-related and immune-related differentially expressed genes (OIDEGs), and analyze their biological functions. Correlation analysis inferred OIDEGs-related differentially expressed lncRNAs (OIDELs) and infiltrating immune cells (OIICs) to construct an immunoregulatory network. Results Differential immune score and immune cell infiltration were determined between two groups, and 10 OIDEGs with diverse biological function annotations were identified and verified. A lncRNA-gene-immunocyte regulatory network further revealed 10 OIDEGs, 41 OIDELs and 7 OIICs that were highly correlated. Among them, CD1E and STAT3 were predicted as hub genes whether at the expression level or interaction level. cDCs emerged as having the most prominent differences and the highest degree of connectivity. FO393414.3, AC096734.1, LINC01137 and DLX6-AS1 with the greatest number of OIDEGs were thought to be more likely to participate in immunoregulation of OLF. Conclusion This is the first research to preliminarily elucidate OLF-related immunocyte infiltration landscape and immune-associated transcriptome signatures based on bioinformatic strategies and real-world data, which may provide compelling insights into the pathogenesis and therapeutic targets of OLF.

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MiR-490-3p inhibits osteogenic differentiation in thoracic ligamentum flavum cells by targeting FOXO1

Cited by 18 publications

References 39 publications

Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions

Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions

miR‐490: A potential biomarker and therapeutic target in cancer and other diseases

Integrating Bioinformatic Strategies with Real-World Data to Infer Distinctive Immunocyte Infiltration Landscape and Immunologically Relevant Transcriptome Fingerprints in Ossification of Ligamentum Flavum

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