Role of miR-199a-5p in osteoblast differentiation by targeting TET2

Qi, Xiangbei; Jia, Bei; Wang, Wei; Xu, Guohui; Guo, Jichao; Li, Xu; Liu, Jianning

doi:10.1016/j.gene.2019.144193

Cited by 19 publications

(11 citation statements)

References 39 publications

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“…In the present study, VSMCs were transfected with a miR-199a-5p inhibitor, after which, the expression levels of the contractile markers SM22α, SMA, calponin and MYH11 were downregulated, suggesting that VSMCs switched to a synthetic phenotype. Conversely, it has previously been reported that miR-199a-5p upregulation may promote cell proliferation and metastasis in cervical carcinoma ( 21 ), and miR-199a-5p downregulation could inhibit osteoblast differentiation ( 5 ). Therefore, the function of miR-199a-5p may vary in different cell types.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs/miRs) exhibit different expression levels in varicose veins compared with in normal veins ( 4 ). Notably, miR-199a-5p has been reported to participate in several pathological processes, such as osteoclast differentiation ( 5 ), spinal cord injury ( 6 ) and tumor proliferation ( 7 ). In addition, overexpression of miR-199a-5p has been shown to promote pulmonary artery hypertension by downregulating Smad3 in a previous study ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

“…miR-199a-5p can suppress mRNA expression by directly targeting the 3′-untranslated region (3′-UTR) ( 5 , 6 , 8 , 9 ). Notably, forkhead box C2 (FOXC2) is a predicted target of miR-199a-5p ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MicroRNA‑199a‑5p regulates FOXC2 to control human vascular smooth muscle cell phenotypic switch

Cao

Zhong-wen²,

Wang

et al. 2021

Mol Med Rep

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Varicose veins are among the most common disorders of the vascular system; however, the pathogenesis of varicose veins remains unclear. The present study aimed to investigate the roles of microRNA (miR)-199a-5p in varicose veins and in the phenotypic transition of vascular smooth muscle cells (VSMCs). Bioinformatics analysis confirmed that miR-199a-5p had target sites on the forkhead box C2 (FOXC2) 3'-untranslated region. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to detect the expression levels of miR-199a-5p and FOXC2 in varicose vein and normal great saphenous vein tissues. Cell Counting Kit-8 and Transwell migration assays were performed to validate the effects of miR-199a-5p on VSMCs. Contractile markers, such as smooth muscle 22α, calponin, smooth muscle actin and myosin heavy chain 11 were used to detect phenotypic transition. RT-qPCR revealed that miR-199a-5p was downregulated in varicose veins compared with expression in normal great saphenous veins, whereas FOXC2 was upregulated in varicose veins. In addition, biomarkers of the VSMC contractile phenotype were downregulated in varicose veins. Overexpression of miR-199a-5p by mimics suppressed VSMC proliferation and migration, whereas depletion of miR-199a-5p enhanced VSMC proliferation and migration. Notably, the effects caused by miR-199a-5p could be reversed by FOXC2 overexpression. Dual luciferase reporter analysis confirmed that FOXC2 was a target of miR-199a-5p. In conclusion, miR-199a-5p may be a novel regulator of phenotypic switching in VSMCs by targeting FOXC2 during varicose vein formation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA‑199a‑5p regulates FOXC2 to control human vascular smooth muscle cell phenotypic switch

Cao

Zhong-wen²,

Wang

et al. 2021

Mol Med Rep

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“…This observation was associated with TET2 upregulation and a decrease in osteoblast differentiation. Conversely, miR-199a-5p upregulation and subsequent TET2 downregulation were associated with better bone development and upregulation of genes involved in the osteogenesis process [66].…”

Section: Mirsmentioning

confidence: 94%

The Potential Equivalents of TET2 Mutations

Pașca

Jurj

Zdrenghea

et al. 2021

Cancers

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TET2 is a dioxygenase dependent on Fe2+ and α-ketoglutarate which oxidizes 5-methylcytosine (5meC) to 5-hydroxymethylcytosine (5hmeC). TET proteins successively oxidize 5mC to yield 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Among these oxidized methylcytosines, 5fC and 5caC are directly excised by thymine DNA glycosylase (TDG) and ultimately replaced with unmethylated cytosine. Mutations in TET2 have been shown to lead to a hypermethylated state of the genome and to be responsible for the initiation of the oncogenetic process, especially in myeloid and lymphoid malignancies. Nonetheless, this was also shown to be the case in other cancers. In AML, TET2 mutations have been observed to be mutually exclusive with IDH1, IDH2, and WT1 mutations, all of them showing a similar impact on the transcription profile of the affected cell. Because of this, it is possible that TET2/IDH1/2/WT1 mutated AML could be considered as having similar characteristics between each other. Nonetheless, other genes also interact with TET2 and influence its effect, thus making it possible that other signatures exist that would mimic the effect of TET2 mutations. Thus, in this review, we searched the literature for the genes that were observed to interact with TET2 and classified them in the following manner: transcription alteration, miRs, direct interaction, posttranslational changes, and substrate reduction. What we propose in the present review is the potential extension of the TET2/IDH1/2/WT1 entity with the addition of certain expression signatures that would be able to induce a similar phenotype with that induced by TET2 mutations. Nonetheless, we recommend that this approach be taken on a disease by disease basis.

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“…Several investigations have shown that miRNAs are mentioned in the osteoblast differentiation of stem cells. For example, miR-199a-5p controls the osteogenic induction of bone marrow mesenchymal stem cells by targeting TET2 [ 17 ]. In addition, miR-450b promotes osteoblast induction in vitro and strength bone generation in vivo by targeting the BMP3 signaling pathway [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

miR-125a-5p Regulates Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells under Oxidative Stress

Liu²,

et al. 2021

BioMed Research International

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Adipose-derived mesenchymal stem cells (ADSCs) are a well-recognized multilineage stem cell with vital clinical feasibility for tissue regeneration. Extensive evidence indicates that oxidative stress and microRNAs (miRNAs/miRs) play an important role in the osteoinduction of adipose-derived mesenchymal stem cells. In this study, we investigated the mechanism of miR-125a-5p in regulating the osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs) under oxidative stress. The expression of miR-125a-5p lessened gradually during the osteogenic differentiation of hADSCs. Relative to the negative group, the expression levels of runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osterix in the miR-125a-5p group were marked lower than those in the miR-125a-5p inhibitor group. The levels of p16, p21, p53, miR-125a-5p, and ROS during osteoinduction of hADSCs were assessed in vitro under oxidative stress and were observed to be upregulated. Further experiments showed that oxidative stress and miR-125a-5p together suppressed the expression of VEGF during osteogenic differentiation of hADSCs and that the inhibition of miR-125a-5p reversed the effect of oxidative stress. In short, our study indicated that miR-125a-5p is induced under oxidative stress and inhibits the expression of VEGF, leading to the reduction of osteogenic differentiation of hADSCs. Our outcomes showed that miR-125a-5p could be a potential clinical target for bone repairing.

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Role of miR-199a-5p in osteoblast differentiation by targeting TET2

Cited by 19 publications

References 39 publications

MicroRNA‑199a‑5p regulates FOXC2 to control human vascular smooth muscle cell phenotypic switch

MicroRNA‑199a‑5p regulates FOXC2 to control human vascular smooth muscle cell phenotypic switch

The Potential Equivalents of TET2 Mutations

miR-125a-5p Regulates Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells under Oxidative Stress

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