The members of the integrin αv (ITGAV) family are widely expressed on many types of tumors and have been reported to be involved into angiogenesis, tumor metastases, and multicellular radioresistance. Osteosarcoma (OS) is the most common primary malignant bone tumor and the role of ITGAV in OS needs to be further elucidated. MicroRNAs are aberrantly expressed in a variety of cancers. Thus, the authors collected OS tissues (n = 15) and corresponding paracancerous tissues (n = 15) and found that the expression of miR-548c-3p was significantly downregulated in OS tissues and cell lines 143B, SaoS2, and HOS when compared to the corresponding paracancerous tissues and human osteoblast cell line hFOB (OB3), respectively. In addition, the authors identified that miR-548c-3p could directly target the 3'-untranslated region of ITGAV, and miR-548c-3p overexpression inhibits the mRNA and protein levels of ITGAV, which were confirmed by the luciferase reporter assays. Interestingly, they also uncovered that miR-548c-3p overexpression or knockdown of ITGAV remarkably suppressed cell vitality and promoted apoptosis and G2/M cell cycle arrest, leading to abrogating the ability of colony formation. The results indicated that the miR-548c-3p, similar to the target agents against integrin αv in clinical trials, could negatively regulate the ITGAV and be a promising tumor therapeutic target.
Macrophages (Mφs) are master regulators of the immune response and may serve as therapeutic targets in aging societies. This study aimed to determine the function of M1Mφ‐exosomes (Exos) in the development of osteoporosis (OP) and the involvement of microRNA (miR)‐98 and dual specificity phosphatase 1 (DUSP1). A murine model of OP was established using ovariectomies (OVX). Bone loss was observed in OVX‐treated mice, as manifested by reduced bone mineral density and decreased number of bone trabecula. The bone loss was further aggravated by treatment with M1Mφ‐Exos. Exos also suppressed osteogenic differentiation of MC3T3‐E1 cells. miRNA microarray analysis revealed that the miR‐98 level was notably upregulated in cells after Exo treatment, and DUSP1 was confirmed as a target of miR‐98. Meanwhile, downregulation of miR‐98 or upregulation of DUSP1 restored the osteogenic differentiation ability of MC3T3‐E1 cells. In addition, upregulation of DUSP1 reduced bone loss in murine bone tissues and suppressed JNK phosphorylation. In summary, M1Mφ‐derived exosomal miR‐98 exacerbates bone loss and OP by downregulating DUSP1 and activating the JNK signaling pathway. miR‐98 may therefore serve as a therapeutic target in OP management.
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