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 ... -  《-》

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 ... -  《-》

MicroRNA-340-5p suppresses osteosarcoma development by down-regulating the Wnt/β-catenin signaling pathway via targeting the STAT3 gene.

Rongxin S ，Pengfei L ，Li S ，Xiaochen J ，Yihe H ... -  《-》

MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2.

Liang TS ，Zheng YJ ，Wang J ，Zhao JY ，Yang DK ，Liu ZS ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Silencing microRNA-27a inhibits proliferation and invasion of human osteosarcoma cells through the SFRP1-dependent Wnt/β-catenin signaling pathway.

Osteosarcoma is the most common malignant tumor of bone with a high potential for metastasis. Importantly, microRNA-27a (miR-27a) is involved in the progression of osteosarcoma. The present study aims to discuss the effects of miR-27a and its target gene secreted frizzled related protein 1 (SFRP1) on proliferation and invasion of human osteosarcoma cells via Wnt/β-catenin signaling pathway. The expression of miR-27a and SFRP1 in osteosarcoma tissues and cells was detected, followed by identification of their relations. Subsequently, miR-27a mimic, miR-27a inhibitor, or siRNA against SFRP1 were introduced into cells (HOS and U2OS) to investigate their role in cell proliferation and invasion. The expression of Wnt/β-catenin signaling pathway-related gene was analyzed to further uncover the regulatory mechanism of miR-27a. The osteosarcoma tissues and cells exhibited elevated miR-27 expression and reduced SFRP1 expression. SFRP1 was verified to be a target gene of miR-27a. Meanwhile, silenced miR-27a inhibited proliferation and invasion of human osteosarcoma cells. Finally, silencing miR-27a inhibited the activation of Wnt/β-catenin signaling pathway, evidenced by reduced β-catenin expression. Our study draws a conclusion that silencing miR-27a dampens osteosarcoma progression, which might be achieved through the inactivation of the Wnt/β-catenin signaling pathway by up-regulating SFRP1.

Mu Y ，Zhang L ，Chen X ，Chen S ，Shi Y ，Li J ... -  《-》