Dataset Information

H19 lncRNA regulates keratinocyte differentiation by targeting miR-130b-3p.

ABSTRACT: Aberrant differentiation of keratinocytes has been demonstrated to be associated with a number of skin diseases. A growing number of studies have showed that long noncoding RNAs (lncRNAs) have an important part in gene regulation, however, the role of lncRNAs in keratinocyte differentiation remains to be largely unknown. In the present study, we demonstrated that lncRNA-H19 act as an endogenous 'sponge', which binds directly to miR-130b-3p and therefore inhibits its activity on Dsg1. MiR-130b-3p was illustrated to inhibit keratinocyte differentiation by targeting Dsg1. H19 regulates Dsg1 expression and the consequent keratinocyte differentiation through miR-130b-3p. Our study casts light on a novel regulatory model of keratinocyte differentiation, which may provide new therapeutic targets of skin diseases.

SUBMITTER: Li CX

PROVIDER: S-EPMC5775403 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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H19 lncRNA regulates keratinocyte differentiation by targeting miR-130b-3p.

Li Chun-Xiao CX Li Hua-Guo HG Huang Lin-Ting LT Kong Yu-Wei YW Chen Fu-Ying FY Liang Jian-Yin JY Yu Hong H Yao Zhi-Rong ZR

Cell death & disease 20171130 11

Aberrant differentiation of keratinocytes has been demonstrated to be associated with a number of skin diseases. A growing number of studies have showed that long noncoding RNAs (lncRNAs) have an important part in gene regulation, however, the role of lncRNAs in keratinocyte differentiation remains to be largely unknown. In the present study, we demonstrated that lncRNA-H19 act as an endogenous 'sponge', which binds directly to miR-130b-3p and therefore inhibits its activity on Dsg1. MiR-130b-3p ...[more]

PMID: 29192645

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Project description:BackgroundProper control of the lineage bias of megakaryocytic and erythroid progenitor cells (MEPs) is of significant importance, the disorder of which will lead to abnormalities in the number and function of platelets and erythrocytes. Unfortunately, the signaling pathways regulating MEP differentiation largely remain to be elucidated. This study aimed to analyze the role and the underlying molecular mechanism of miR-1915-3p in megakaryocytic and erythroid differentiation.MethodsWe utilized miRNA mimics and miRNA sponge to alter the expression of miR-1915-3p in megakaryocytic and/or erythroid potential cells; siRNA and overexpression plasmid to change the expression of SOCS4, a potential target of miR-1915-3p. The expression of relevant surface markers was detected by flow cytometry. We scanned for miR-1915-3p target genes by mRNA expression profiling and bioinformatic analysis, and confirmed the targeting by dual-luciferase reporter assay, western blot and gain- and lost-of-function studies. One-way ANOVA and t-test were used to analyze the statistical significance.ResultsIn this study, overexpression or knockdown of miR-1915-3p inhibited or promoted erythroid differentiation, respectively. Accordingly, we scanned for miR-1915-3p target genes and confirmed that SOCS4 is one of the direct targets of miR-1915-3p. An attentive examination of the endogenous expression of SOCS4 during megakaryocytic and erythroid differentiation suggested the involvement of SOCS4 in erythroid/megakaryocytic lineage determination. SOCS4 knockdown lessened erythroid surface markers expression, as well as improved megakaryocytic differentiation, similar to the effects of miR-1915-3p overexpression. While SOCS4 overexpression resulted in reversed effects. SOCS4 overexpression in miR-1915-3p upregulated cells rescued the effect of miR-1915-3p.ConclusionsmiR-1915-3p acts as a negative regulator of erythropoiesis, and positively in thrombopoiesis. SOCS4 is one of the key mediators of miR-1915-3p during the differentiation of MEPs.

Dataset Information

H19 lncRNA regulates keratinocyte differentiation by targeting miR-130b-3p.

Publications

H19 lncRNA regulates keratinocyte differentiation by targeting miR-130b-3p.

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