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MiRNA-140-3p affects the proliferation and metastasis of osteosarcoma via the UBE2C/PI3K-Akt axis
Xu Yang1, Yubo Xiang2, Haoran Liu3
1Department of Rehabilitation Medicine, General Hospital of Northern Theater Command, Shenyang, China.
Abstract:
The data of scRNA-seq in specific databases were analyzed by bioinformatics. The expression level of miR-140-3p in osteosarcoma cells was detected using qRT-PCR, and the correlation between the expression level of miR-140-3p and the survival of tumor patients was analyzed using a database. A series of experiments were conducted to explore the role of miR-140-3p in osteosarcoma cells. Database prediction of target genes, dual luciferase reporter gene experiments, and a series of in vivo and in vitro experiments were used to explore the related mechanisms of miR-140-3p's influence on osteosarcoma proliferation and metastasis. MiR-140-3p was significantly lower expressed in osteosarcoma cells. Low expression of miR-140-3p is closely associated with poor survival of tumor patients. In vitro and in vivo, overexpression of miR-140-3p can significantly inhibit the proliferation and metastasis of osteosarcoma cells, hinder the cycle process of osteosarcoma cells, and promote the apoptosis of osteosarcoma cells. In vivo, overexpression of miR-140-3p can significantly inhibit subcutaneous tumor formation and lung metastasis of osteosarcoma cells in nude mice. Knockdown of miR-140-3p has the opposite effect in vivo and in vitro. Mechanistically, UBE2C is a direct target gene of miR-140-3p, and UBE2C is highly expressed in osteosarcoma cells and most cancer tissues, and is associated with poor survival of tumor patients. The interaction between miR-140-3p and UBE2C can affect the activation of the PI3K/Akt signaling pathway, which significantly changes the malignant biological characteristics of osteosarcoma cells in vivo and in vitro. The miR-140-3p/UBE2C/PI3K-Akt axis could be a promising target for treatment.
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