MiR-15b and miR-322 inhibit SETD3 expression to repress muscle cell differentiation

Zhao, Mengjie; Xie, Jun; Shu, Wen-Jie; Wang, Hongyan; Bi, Jianping; Jiang, Wei; Du, Hai-Ning

doi:10.1038/s41419-019-1432-5

Cited by 24 publications

(15 citation statements)

References 38 publications

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“…They play critical regulatory roles in posttranscription in gene expressions by targeting specific mRNAs for destabilizing the mRNA, repressing protein production, and translational silencing [6]. With this powerful regulatory function, miRNAs contribute to various biological processes including proliferation [7], differentiation [8], and apoptosis [7]. Abundant evidences have showed that miRNAs are involved in pathogenesis of many diseases, especially tumor development [9].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-30-3p Suppresses Inflammatory Factor-Induced Endothelial Cell Injury by Targeting TCF21

Zhou

Chen

Zhang

et al. 2019

Mediators of Inflammation

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Atherosclerosis is one of the leading causes of mortality worldwide. Growing evidence suggested that miRNAs contributed to the progression of atherosclerosis. miR-30-5p was found involved in various diseases. However, the role of miR-30-5p in regulation of atherosclerosis is not known. Here, we aim to investigate the effects of miR-30-5p on regulating the progression of atherosclerosis. The expression levels of miR-30-5p in serum collected from atherosclerosis patients and normal healthy people were analyzed by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway bioinformatics were carried out to reveal the possible signaling pathways involved in the mode of action of miR-30-5p. A potential target gene of miRNA-30-5p was searched and examined by a luciferase reporter assay. ELISA, Western blot, proliferation, and flow cytometry assays were performed to assess the biological functional role of miR-30-5p in vitro. Also, an in vitro monocyte-endothelial cell coculture model was used to study the functional role of miR-30-5p in atherosclerosis. We found that miR-30-5p was significantly decreased in serum samples from atherosclerosis patients compared with control subjects. GO and KEGG analysis results showed that miR-30-5p is highly associated with genetic profile of cardiovascular disease. TCF21 was verified as a target gene of miR-30-5p. Overexpression of miR-30-5p in THP-1 not only protected endothelial cell viability but also inhibited endothelial cell apoptosis, and similar results were observed in cells with that of TCF21 knocked down. Moreover, miR-30-5p decreased the expression levels of lactate dehydrogenase (LDH) and tumor necrosis factor-α (TNF-α) and reduced reactive oxygen species (ROS) accumulation. NF-κB and MAPK/p38 pathways played an indispensable role in the protection ability of miR-30-5p against atherosclerosis. Our results reveal that miR-30-5p suppresses the progression of atherosclerosis through targeting TCF21 in vitro. Therefore, the miR-30-5p-TCF21-MAPK/p38 signaling pathway may be a potential biomarker or therapeutic target in atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-30-3p Suppresses Inflammatory Factor-Induced Endothelial Cell Injury by Targeting TCF21

Zhou

Chen

Zhang

et al. 2019

Mediators of Inflammation

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“…Muscle-specific miRNAs included miR-1, miR-133a/b, and miR-206, which were involved in myoblast proliferation and differentiation by regulating the expression of target genes, such as histone deacetylase 4, serum response factor, the myogenic differentiation family, and other myogenic transcriptional factors [9][10][11]. Other non-specific muscle miRNAs have also been involved in the regulation of muscle growth and development, such as miR-17, miR-19, miR-15b, miR-322, miR-208b, miR-26a, miR-30, miR-128a, miR-203a, miR-214, and miR-3906 [12][13][14][15]. For example, miR-26a promoted myoblast differentiation by regulating the expression of target genes Smad1 and Smad4 [16].…”

Section: Introductionmentioning

confidence: 99%

Altered miRNA and mRNA Expression in Sika Deer Skeletal Muscle with Age

Jia

Liu

et al. 2020

Genes

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Studies of the gene and miRNA expression profiles associated with the postnatal late growth, development, and aging of skeletal muscle are lacking in sika deer. To understand the molecular mechanisms of the growth and development of sika deer skeletal muscle, we used de novo RNA sequencing (RNA-seq) and microRNA sequencing (miRNA-seq) analyses to determine the differentially expressed (DE) unigenes and miRNAs from skeletal muscle tissues at 1, 3, 5, and 10 years in sika deer. A total of 51,716 unigenes, 171 known miRNAs, and 60 novel miRNAs were identified based on four mRNA and small RNA libraries. A total of 2,044 unigenes and 11 miRNAs were differentially expressed between adolescence and juvenile sika deer, 1,946 unigenes and 4 miRNAs were differentially expressed between adult and adolescent sika deer, and 2,209 unigenes and 1 miRNAs were differentially expressed between aged and adult sika deer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that DE unigenes and miRNA were mainly related to energy and substance metabolism, processes that are closely associate with the growth, development, and aging of skeletal muscle. We also constructed mRNA–mRNA and miRNA–mRNA interaction networks related to the growth, development, and aging of skeletal muscle. The results show that mRNA (Myh1, Myh2, Myh7, ACTN3, etc.) and miRNAs (miR-133a, miR-133c, miR-192, miR-151-3p, etc.) may play important roles in muscle growth and development, and mRNA (WWP1, DEK, UCP3, FUS, etc.) and miRNAs (miR-17-5p, miR-378b, miR-199a-5p, miR-7, etc.) may have key roles in muscle aging. In this study, we determined the dynamic miRNA and unigenes transcriptome in muscle tissue for the first time in sika deer. The age-dependent miRNAs and unigenes identified will offer insights into the molecular mechanism underlying muscle development, growth, and maintenance and will also provide valuable information for sika deer genetic breeding.

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“…miR-322/-503 was required in myoblast differentiation miR-322/-503 was revealed to promote cardiac differentiation by targeting Celf1 in early cardiac progenitor cells 39 , but its function in myoblast differentiation was still under debate 40,41 . We performed β-galactosidase staining on miR-322/-503 lacZ knock-in mouse E10.5 embryos.…”

Section: Resultsmentioning

confidence: 99%

“…The expressions of both miRNAs are under the control of the same cis -elements. miR-322/-503 was reported to function mainly in cancer 31 – 33 , angiogenesis 34 , 35 , cardiovascular diseases 36 – 38 , and development fields 39 – 41 . Our previous study demonstrated that miR-322/-503 was enriched in early cardiac progenitors and promoted cardiac differentiation by repressing Celf1 39 .…”

Section: Introductionmentioning

confidence: 99%

“…Our previous study demonstrated that miR-322/-503 was enriched in early cardiac progenitors and promoted cardiac differentiation by repressing Celf1 39 . As to myoblast differentiation, miR-322/-503’s role was under debate: one reference claimed that miR-322/-503 promoted myoblast differentiation by inhibiting cell cycle via targeting Cdc25A 40 , while another one argued that miR-322 inhibited myoblast differentiation by targeting SETD3 41 . Moreover, although miR-322/-503 was proven to target Celf1 during cardiac differentiation, miR-322/-503’s function in DM1 was still illusive.…”

Section: Introductionmentioning

confidence: 99%

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miR-322/-503 rescues myoblast defects in myotonic dystrophy type 1 cell model by targeting CUG repeats

Shen

Feng

et al. 2020

Cell Death Dis

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Myotonic dystrophy type 1 (DM1) is the most common type of adult muscular dystrophy caused by the expanded triple-nucleotides (CUG) repeats. Myoblast in DM1 displayed many defects, including defective myoblast differentiation, ribonuclear foci, and aberrant alternative splicing. Despite many were revealed to function in DM1, microRNAs that regulated DM1 via directly targeting the expanded CUG repeats were rarely reported. Here we discovered that miR-322/-503 rescued myoblast defects in DM1 cell model by targeting the expanded CUG repeats. First, we studied the function of miR-322/-503 in normal C2C12 myoblast cells. Downregulation of miR-322/-503 significantly hindered the myoblast differentiation, while miR-322/-503 overexpression promoted the process. Next, we examined the role of miR-322/-503 in the DM1 C2C12 cell model. miR-322/-503 was downregulated in the differentiation of DM1 C2C12 cells. When we introduced ectopic miR-322/-503 expression into DM1 C2C12 cells, myoblast defects were almost fully rescued, marked by significant improvements of myoblast differentiation and repressions of ribonuclear foci formation and aberrant alternative splicing. Then we investigated the downstream mechanism of miR-322/-503 in DM1. Agreeing with our previous work, Celf1 was proven to be miR-322/-503′s target. Celf1 knockdown partially reproduced miR-322/-503′s function in rescuing DM1 C2C12 differentiation but was unable to repress ribonuclear foci, suggesting other targets of miR-322/-503 existed in the DM1 C2C12 cells. As the seed regions of miR-322 and miR-503 were complementary to the CUG repeats, we hypothesized that the CUG repeats were the target of miR-322/-503. Through expression tests, reporter assays, and colocalization staining, miR-322/-503 was proved to directly and specifically target the expanded CUG repeats in the DM1 cell model rather than the shorter ones in normal cells. Those results implied a potential therapeutic function of miR-322/-503 on DM1, which needed further investigations in the future.

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MiR-15b and miR-322 inhibit SETD3 expression to repress muscle cell differentiation

Cited by 24 publications

References 38 publications

MicroRNA-30-3p Suppresses Inflammatory Factor-Induced Endothelial Cell Injury by Targeting TCF21

MicroRNA-30-3p Suppresses Inflammatory Factor-Induced Endothelial Cell Injury by Targeting TCF21

Altered miRNA and mRNA Expression in Sika Deer Skeletal Muscle with Age

miR-322/-503 rescues myoblast defects in myotonic dystrophy type 1 cell model by targeting CUG repeats

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