Dataset Information

MiR-1281, a p53-responsive microRNA, impairs the survival of human osteosarcoma cells upon ER stress via targeting USP39.

ABSTRACT: MicroRNAs (miRNAs) are small regulatory non-coding RNAs that have been reported to play an important role in a variety of cellular functions. Recent studies indicated that some miRNAs are involved in regulating endoplasmic reticulum (ER) stress adaptation. However, the miRNAs were still unknown in osteosarcoma. In this study, we demonstrated that miR-1281 induced by ER stress promoted cell apoptosis and decreased ER stress adaptation of osteosarcoma in vitro and in vivo. Further mechanistic studies revealed that p53, an important tumor suppressor, directly bound to the promoter of miR-1281, leading to its increase under ER stress. Additionally, our data suggest that USP39 was the target of miR-1281 and participated in ER stress-induced cell apoptosis. Thus, our findings suggest a new role for miR-1281 in osteosarcoma and suggest that the p53-dependent, miR-1281-mediated USP39 pathway inhibits the survival of human osteosarcoma cells under ER stress.

SUBMITTER: Jiang J

PROVIDER: S-EPMC6176178 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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MiR-1281, a p53-responsive microRNA, impairs the survival of human osteosarcoma cells upon ER stress via targeting USP39.

Jiang Jian J Ma Binbin B Li Xiaojie X Jin Wenlong W Han Chuanchun C Wang Ling L Wang Hong H

American journal of cancer research 20180901 9

MicroRNAs (miRNAs) are small regulatory non-coding RNAs that have been reported to play an important role in a variety of cellular functions. Recent studies indicated that some miRNAs are involved in regulating endoplasmic reticulum (ER) stress adaptation. However, the miRNAs were still unknown in osteosarcoma. In this study, we demonstrated that miR-1281 induced by ER stress promoted cell apoptosis and decreased ER stress adaptation of osteosarcoma <i>in vitro</i> and <i>in vivo</i>. Further me ...[more]

PMID: 30323969

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Project description:Skeletal myogenesis is a regulated process in which mononucleated cells, the myoblasts, undergo proliferation and differentiation. Upon differentiation, the cells align with each other, and subsequently fuse to form terminally differentiated multinucleated myotubes. Previous reports have identified the protein osteoglycin (Ogn) as an important component of the skeletal muscle secretome, which is expressed differentially during muscle development. However, the posttranscriptional regulation of Ogn by microRNAs during myogenesis is unknown. Bioinformatic analysis showed that miR-155 potentially targeted the Ogn transcript at the 3´-untranslated region (3´ UTR). In this study, we tested the hypothesis that miR-155 inhibits the expression of the Ogn to regulate skeletal myogenesis. C2C12 myoblast cells were cultured and miR-155 overexpression or Ogn knockdown was induced by transfection with miR-155 mimic, siRNA-Ogn, and negative controls with lipofectamine for 15 hours. Near confluence (80-90%), myoblasts were induced to differentiate myotubes in a differentiation medium. Luciferase assay was used to confirm the interaction between miR-155 and Ogn 3'UTR. RT-qPCR and Western blot analyses were used to confirm that the differential expression of miR-155 correlates with the differential expression of myogenic molecular markers (Myh2, MyoD, and MyoG) and inhibits Ogn protein and gene expression in myoblasts and myotubes. Myoblast migration and proliferation were assessed using Wound Healing and MTT assays. Our results show that miR-155 interacts with the 3'UTR Ogn region and decrease the levels of Ogn in myotubes. The overexpression of miR-155 increased MyoG expression, decreased myoblasts wound closure rate, and decreased Myh2 expression in myotubes. Moreover, Ogn knockdown reduced the expression levels of MyoD, MyoG, and Myh2 in myotubes. These results reveal a novel pathway in which miR-155 inhibits Ogn expression to regulate proliferation and differentiation of C2C12 myoblast cells.

Dataset Information

MiR-1281, a p53-responsive microRNA, impairs the survival of human osteosarcoma cells upon ER stress via targeting USP39.

Publications

MiR-1281, a p53-responsive microRNA, impairs the survival of human osteosarcoma cells upon ER stress via targeting USP39.

Similar Datasets

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