Dataset Information

The miR-193a-3p-MAP3k3 Signaling Axis Regulates Substrate Topography-Induced Osteogenesis of Bone Marrow Stem Cells.

ABSTRACT: Substrate topographical features induce osteogenic differentiation of bone marrow stem cells (BMSCs), but the underlying mechanisms are unclear. As microRNAs (miRNAs) play key roles in osteogenesis and bone regeneration, it would be meaningful to elucidate the roles of miRNAs in the intracellular signaling cascade of topographical cue-induced osteogenic differentiation. In this study, the miRNA expression profile of the topographical feature-induced osteogenic differentiation group is different from that of the chemical-factors-induced osteogenic differentiation group. miR-193a-3p is sensitive to substrate topographical features and its downregulation enhances osteogenic differentiation only in the absence of osteogenesis-inducing medium. Also, substrate topographical features specifically activate a nonclassical osteogenetic pathway-the mitogen-activated protein kinase (MAPK) pathway. Loss- and gain-of-function experiments demonstrate that miR-193a-3p regulates the MAPK pathway by targeting the MAP3k3 gene. In conclusion, this data indicates that different osteogenic-lineage-related intracellular signaling cascades are triggered in BMSCs subjected to biophysical or chemical stimulation. Moreover, the miR-193a-3p-MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic lineage specification of BMSCs, and hence may be a promising molecular target for bone regenerative therapies.

SUBMITTER: Lv Y

PROVIDER: S-EPMC6947707 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The miR-193a-3p-MAP3k3 Signaling Axis Regulates Substrate Topography-Induced Osteogenesis of Bone Marrow Stem Cells.

Lv Yan Y Huang Ying Y Xu Mingming M Heng Boon Chin BC Yang Congchong C Cao Cen C Hu Zhewen Z Liu Wenwen W Chi Xiaopei X Gao Min M Zhang Xuehui X Wei Yan Y Deng Xuliang X

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20191113 1

Substrate topographical features induce osteogenic differentiation of bone marrow stem cells (BMSCs), but the underlying mechanisms are unclear. As microRNAs (miRNAs) play key roles in osteogenesis and bone regeneration, it would be meaningful to elucidate the roles of miRNAs in the intracellular signaling cascade of topographical cue-induced osteogenic differentiation. In this study, the miRNA expression profile of the topographical feature-induced osteogenic differentiation group is different ...[more]

PMID: 31921551

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Project description:Lung adenocarcinoma (LUAD) remains the most common subtype of lung malignancy. Cuproptosis is a newly identified cell death which could regulate tumor cell proliferation and progression. Long non-coding RNAs (lncRNAs) are key molecules and potential biomarkers for diagnosing and treating various diseases. However, the effects of cuproptosis-related lncRNAs on LUAD are still unclear. In our study, 7 cuproptosis-related lncRNAs were selected to establish a prognostic model using univariate Cox regression analysis, LASSO algorithm, and multivariate analysis. Furthermore, we evaluated AC008764.2, AL022323.1, ELN-AS1, and LINC00578, which were identified as protective lncRNAs, while AL031667.3, AL606489.1, and MIR31HG were identified as risk lncRNAs. The risk score calculated by the prognostic model proved to be an effective independent factor compared with other clinical features by Cox regression analyses [univariate analysis: hazard ratio (HR) = 1.065, 95% confidence interval (CI) = 1.043-1.087, P < 0.001; multivariate analysis: HR = 1.067, 95% CI = 1.044-1.091, P < 0.001]. In addition, both analyses (ROC and nomogram) were used to corroborate the accuracy and reliability of this signature. The correlation between cuproptosis-related lncRNAs and immune microenvironment was elucidated, where 7 immune cells and 8 immune-correlated pathways were found to be differentially expressed between two risk groups. Furthermore, our results also identified and verified the ceRNA of cuproptosis-related lncRNA MIR31HG/miR-193a-3p/TNFRSF21 regulatory axis using bioinformatics tools. MIR31HG was highly expressed in LUAD specimens and some LUAD cell lines. Inhibition of MIR31HG clearly reduced the proliferation, migration, and invasion of the LUAD cells. MIR31HG showed oncogenic features via sponging miR-193a-3p and tended to positively regulate TNFRSF21 expression. In a word, lncRNA MIR31HG acts as an oncogene in LUAD by targeting miR-193a-3p to modulate TNFRSF21, which may be beneficial to the gene therapy of LUAD.

Dataset Information

The miR-193a-3p-MAP3k3 Signaling Axis Regulates Substrate Topography-Induced Osteogenesis of Bone Marrow Stem Cells.

Publications

The miR-193a-3p-MAP3k3 Signaling Axis Regulates Substrate Topography-Induced Osteogenesis of Bone Marrow Stem Cells.

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