Search

Abstract: MicroRNAs (miRNAs) have been shown to be important regulators in the pathogenesis of osteoarthritis (OA). The objective of this study was to determine the expression levels of miR-483, miR-483*, their host gene (Igf2) and other cytokines in a murine model of OA. The expression of miR-483 was significantly up-regulated in old mouse and in all of the operation groups, particularly the group assessed 1 week after surgery. The expression of miR-483* was significantly increased in the old mouse group and the group assessed 5 weeks after surgery. The expression of miR-483 was negatively correlated with the expression of (mRNA) Bmp7 and TgfB and positively correlated with Mmp13 by Pearson correlation analysis, while miR-483* was positively correlated with Il1B. Surprisingly, there was no correlation between the expression of either miR-483 or miR-483* and Igf2. This study shows that the expression of miR-483 and miR-483* is up-regulated in murine OA. These data suggest that miR-483 and miR-483* may play critical roles in early and later pathogenesis of OA, respectively, without the involvement of their host gene Igf2. [Copyright &y& Elsevier]

Abstract: MicroRNAs (miRNAs) are endogenous noncoding RNAs that downregulate gene expression by inhibiting translation or promoting mRNA degradation. Although over one-third of miRNAs are located within the intronic regions of transcription units, the expression of such “intron-derived” (or “intronic”) miRNAs and their relationship with their host gene remain a mystery. Here, we show that miR-483-5p, which is located within the second intron of the insulin-like growth factor (Igf2) gene, is downregulated in mouse Hepa1–6 cells in a direct correlation with the Igf2 transcript by chromeceptin, an inhibitor of Igf2 at the transcriptional level. Furthermore, miR-483-5p overexpression and knockdown regulates the suppressor of cytokine signalling 3 (Socs3) and Igf2 mRNAs, respectively. Finally, Socs3, a key putative leptin-resistant factor in obesity, is identified as a direct target of miR-483-5p. These data suggest that miR-483-5p can be coexpressed together with its host gene, Igf2, and revealed the link between this miRNA and the IGF2 growth factor. In addition, these observations not only provide supporting evidence for the codependent expression of intronic miRNAs and their host genes in vitro, but also give insight into the role of miR-483-5p in metabolism regulation and tumourigenesis. [ABSTRACT FROM AUTHOR]