miR-425-5p decreases LncRNA MALAT1 and TUG1 expressions and suppresses tumorigenesis in osteosarcoma via Wnt/β-catenin signaling pathway.

Multiple miRNAs have been recognized as critical regulators in osteosarcoma (OS) carcinogenesis. miR-425-5p was demonstrated to be downregulated in the serum of OS patients. However, the detailed roles of miR-425-5p in OS progression and its underlying molecular mechanism are far from being addressed. In our study, the reduced expression of miR-425-5p was observed in OS tissues and cells. Functional analyses showed that miR-425-5p overexpression suppressed OS cell proliferation, invasion and migration in vitro. Moreover, miR-425-5p upregulation decreased the expressions of MALAT1 and TUG1 in OS cells via directly binding them. miR-425-5p upregulation strikingly abrogated the activation of Wnt/β-catenin signaling pathway induced by MALAT1 and TUG1 overexpression in OS cells. Finally, we validated that miR-425-5p hindered OS tumor growth, and suppressed MALAT1 and TUG1 expressions and the Wnt/β-catenin signaling pathway in vivo. Our findings concluded that miR-425-5p suppressed the tumorigenesis of OS via decreasing MALAT1 and TUG1 expressions through inactivation of the Wnt/β-catenin signaling pathway, contributing to a better understanding of the molecular mechanism of the tumorigenesis of OS.

Yang G ，Zhang C ，Wang N ，Chen J ... -  《-》

Down-regulation of microRNA-31-5p inhibits proliferation and invasion of osteosarcoma cells through Wnt/β-catenin signaling pathway by enhancing AXIN1.

Recently, the role of microRNA-31-5p (miR-31-5p) in gene expression regulation has been reported in various cancers. Studies have shown that Wnt/β-catenin signaling pathway is involved in the proliferation and invasion of osteosarcoma (OS) cells. Therefore, this study aims to probe into the regulatory role of miR-31-5p targeting AXIN1 in OS cells through Wnt/β-catenin signaling pathway. Firstly, microarray expression profiles were used to screen differentially expressed miRNAs associated with OS. Next, OS and normal fibrous connective tissues as well as OS cell lines were obtained for investigating the role of miR-31-5p on OS. Then, the putative binding sites between miR-31-5p and AXIN1 were predicted and verified. The regulatory effects of miR-31-5p on proliferation and invasion as well as tumorigenic potential of OS cells targeting AXIN1 were also analyzed. Besides, the relationship between miR-31-5p and Wnt/β-catenin signaling pathway was assessed by immunofluorescence staining. The microarray dataset GSE63939 showed that miR-31-5p and AXIN1 were involved in OS. miR-31-5p expression increased while the expression of AXIN1 decreased in OS tissues and cells. AXIN1 was identified as a target gene of miR-31-5p, intense expression of which inhibited the transcription of AXIN1. Down-regulated miR-31-5p suppressed proliferation, invasion and tumorigenicity of OS cells through promoting AXIN1. Decreased miR-31-5p activated Wnt/β-catenin signaling pathway, as reflected by increased β-catenin translocation into nuclei, through up-regulating the transcription of AXIN1. All in all, repression of miR-31-5p targets AXIN1 to activate the Wnt/β-catenin signaling pathway, thus suppressing proliferation, invasion and tumorigenicity of OS cells.

Chen X ，Zhong L ，Li X ，Liu W ，Zhao Y ，Li J ... -  《-》

TUG1 promotes osteosarcoma tumorigenesis by upregulating EZH2 expression via miR-144-3p.

Cao J ，Han X ，Qi X ，Jin X ，Li X ... -  《-》

miR-140-5p is negatively correlated with proliferation, invasion, and tumorigenesis in malignant melanoma by targeting SOX4 via the Wnt/β-catenin and NF-κB cascades.

MicroRNAs (miRNAs) have been validated as critical regulators in the development of melanoma. miR-140 was abnormally downregulated in uveal melanoma samples. However, the expression level and roles of miR-140-5p remain unclear in melanoma for now. We speculate that miR-140-5p is abnormally expressed and may play an important role in melanoma. The expressions of miR-140-5p and SOX4 messenger RNA were determined by quantitative real-time polymerase chain reaction assays. Western blot assays were employed to detect the expression levels of SOX4, Ki67, MMP-2, MMP-7, p-β-catenin, c-Myc, cyclin D1, p65, and IκBα. Luciferase reporter assays were employed to elucidate the interaction between SOX4 and miR-140-5p. MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) and transwell invasion assays were applied to evaluate capabilities of cell proliferation and invasion, respectively. Xenograft models of melanoma were established to verify the role and molecular basis of miR-140-5p. Immunohistochemical (IHC) assays were employed to measure the Ki67 and SOX4 at the protein level in xenografted melanoma tissues. Herein, these observations showed that, miR-140-5p was abnormally downregulated in melanoma tissues and cells, while SOX4 was upregulated. miR-140-5p directly targeted SOX4 and inhibited its expression in melanoma cells. miR-140-5p overexpression repressed melanoma cell proliferation and invasion and its effects were partially restored SOX4 overexpression. Moreover, miR-140-5p hindered melanoma growth in vivo by downregulating SOX4. Mechanistically, miR-140-5p suppressed activation of the Wnt/β-catenin and NF-κB pathways by targeting SOX4. Our study concluded that miR-140-5p hindered cell proliferation, invasion, and tumorigenesis by targeting SOX4 via inactivation of the Wnt/β-catenin and NF-κB signaling pathways in malignant melanoma, which provides an underlying molecular mechanism for the treatment for melanoma with miRNAs.

Zhao G ，Yin Y ，Zhao B 《-》

MALAT1 promotes osteosarcoma development by regulation of HMGB1 via miR-142-3p and miR-129-5p.

Liu K ，Huang J ，Ni J ，Song D ，Ding M ，Wang J ，Huang X ，Li W ... -  《-》