The transient expression of miR-203 and its inhibiting effects on skeletal muscle cell proliferation and differentiation

Luo, Wei; H, Wu; Ye, Y; Li, Zhanbiao; Hao, Sha; Kong, Lei; Zheng, Xiaodan; Lin, Senjie; Nie, Qinghua; Zhang, X

doi:10.1038/cddis.2014.289

Cited by 84 publications

(82 citation statements)

References 59 publications

(89 reference statements)

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“…However, few reports have focused on the role of miR-203 in the regulation of osteoblast function and the development of HO. Luo et al 22 has demonstrated that miR-203 represses primary myoblast proliferation and differentiation by targeting c-JUN and MEF2C. In our study, we found a mechanism by which miR-203 is involved in the regulation of the expression of the Runx2 protein in HO tissues.…”

Section: Discussionsupporting

confidence: 66%

miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2

Liu

et al. 2016

Cell Death Dis

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Emerging evidence has indicated that dysregulated microRNAs (miRNAs) have an important role in bone formation. However, the pathophysiological role of miRNAs in traumatic heterotopic ossification (HO) remains to be elucidated. Using gene expression profile analyses and subsequent confirmation with real-time PCR assays, we identified the decreased expression of miRNA-203 (miR-203) and increased expression of Runx2 as responses to the development of traumatic HO. We found that miR-203 expression was markedly higher in primary and recurrent HO tissues than in normal bones. The upregulation of miR-203 significantly decreased the level of Runx2 expression, whereas miR-203 downregulation increased Runx2 expression. Mutation of the putative miR-203-binding sites in Runx2 mRNA abolished miR-203-mediated repression of Runx2 3'-untranslated region luciferase reporter activity, indicating that Runx2 is an important target of miR-203 in osteoblasts. We also found that miR-203 is negatively correlated with osteoblast differentiation. Furthermore, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-203 and decreased by agomir-203. We showed that miR-203 suppresses osteoblast activity by inhibiting the β-catenin and extracellular signal-regulated kinase pathways. Moreover, using a tenotomy mouse HO model, we found an inhibitory role of miR-203 in regulating HO in vivo; pretreatment with antagomiR-203 increased the development of HO. These data suggest that miR-203 has a crucial role in suppressing HO by directly targeting Runx2 and that the therapeutic overexpression of miR-203 may be a potential strategy for treating traumatic HO.

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Section: Discussionsupporting

confidence: 66%

miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2

Liu

et al. 2016

Cell Death Dis

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“…The dual luciferase reporter assay was performed as previously described15. Briefly, for the promoter assays of pri-miRNAs, DF-1 cells were co-transfected with reporter plasmid and E2F1 overexpression vector or control vector, and the TK-Renilla reporter was also co-transfected to each sample as an internal control.…”

Section: Methodsmentioning

confidence: 99%

E2F1-miR-20a-5p/20b-5p auto-regulatory feedback loop involved in myoblast proliferation and differentiation

Luo

et al. 2016

Sci Rep

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miR-17 family microRNAs (miRNAs) are crucial for embryo development, however, their role in muscle development is still unclear. miR-20a-5p and miR-20b-5p belong to the miR-17 family and are transcribed from the miR-17~92 and miR-106a~363 clusters respectively. In this study, we found that miR-20a-5p and miR-20b-5p promoted myoblast differentiation and repressed myoblast proliferation by directly binding the 3′ UTR of E2F transcription factor 1 (E2F1) mRNA. E2F1 is an important transcriptional factor for organism’s normal development. Overexpression of E2F1 in myoblasts promoted myoblast proliferation and inhibited myoblast differentiation. Conversely, E2F1 inhibition induced myoblast differentiation and repressed myoblast proliferation. Moreover, E2F1 can bind directly to promoters of the miR-17~92 and miR-106a~363 clusters and activate their transcription, and E2F1 protein expression is correlated with the expression of pri-miR-17~92 and pri-miR-106a~363 during myoblast differentiation. These results suggested an auto-regulatory feedback loop between E2F1 and miR-20a-5p/20b-5p, and indicated that miR-20a-5p, miR-20b-5p and E2F1 are involved in myoblast proliferation and differentiation through the auto-regulation between E2F1 and miR-20a-5p/20b-5p. These findings provide new insight into the mechanism of muscle differentiation, and further shed light on the understanding of muscle development and muscle diseases.

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“…The commitment of cells to the myogenic lineage depends on the expression of myogenic regulatory factors (MRFs), including: MyoD, Myf5, MyoG, Myogenin and MRF4, [1][2][3][4][5][6][7][8] and microRNAs. [9][10][11][12][13][14] While early myogenesis markers can be also expressed in proliferating cells, late differentiation markers, like myosin heavy chain (MHC), are induced only after cell cycle arrest. 15 The retinoblastoma protein (Rb) and cyclin D, plays a critical role in myoblasts cycle arrest; indeed myocytes and muscle cells lacking Rb fail to exit the cell cycle, [16][17][18][19][20][21][22][23][24][25][26] altering the late phases of skeletal myogenesis.…”

Section: Introductionmentioning

confidence: 99%

TAp63gamma is required for the late stages of myogenesis

Cefalù

Lena

Vojtesek³

et al. 2015

Cell Cycle

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Abbreviations: MRFs, myogenic regulatory factors; Rb, retinoblastoma protein; MHC, myosin heavy chain.p53 family members, p63 and p73, play a role in controlling early stage of myogenic differentiation. We demonstrated that TAp63gamma, unlike the other p53 family members, is markedly up-regulated during myogenic differentiation in murine C2C7 cell line. We also found that myotubes formation was inhibited upon TAp63gamma knock-down, as also indicated by atrophyic myotubes and reduction of myoblasts fusion index. Analysis of TAp63gamma-dependend transcripts identified several target genes involved in skeletal muscle contractility energy metabolism, myogenesis and skeletal muscle autocrine signaling. These results indicate that TAp63gamma is a late marker of myogenic differentiation and, by controlling different sub-sets of target genes, it possibly contributes to muscle growth, remodeling, functional differentiation and tissue homeostasis.

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The transient expression of miR-203 and its inhibiting effects on skeletal muscle cell proliferation and differentiation

Cited by 84 publications

References 59 publications

miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2

miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2

E2F1-miR-20a-5p/20b-5p auto-regulatory feedback loop involved in myoblast proliferation and differentiation

TAp63gamma is required for the late stages of myogenesis

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