MiR-30a inhibits osteolysis by targeting RunX2 in giant cell tumor of bone

Huang, Quan; Jiang, Zhengyu; Meng, Tong; Yin, Huabin; Wang, Jing; Wan, Wei; Cheng, Mo; Yan, Wangjun; Liu, Tielong; Song, Dianwen; Chen, Haiyan; Wu, Zhipeng; Xu, Wei; Li, Zhenxi; Wang, Zhou; Xiao, Jianru

doi:10.1016/j.bbrc.2014.09.076

Cited by 34 publications

(26 citation statements)

References 20 publications

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“…Restoration assays proved that Runx2 is involved in miR30a-mediated regulation of proliferation, migration, and invasion of OS cells. Some papers had described that Runx2 is a target of miR-30a [44,45], but this is the first time that demonstrated that miR-30a could affect proliferation, migration, and invasion by Runx2 in OS cells. Fig.…”

Section: Discussionmentioning

confidence: 95%

MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2

et al. 2015

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Osteosarcoma (OS) is the most common primary malignant bone tumor in young patients. However, treatment paradigms and survival rates have not improved in decades. MicroRNAs have been shown to be critical regulators of physiological homeostasis and pathological process, including bone disease. Nearly half of the microRNA (miRNA) genes are located at genomic regions and fragile sites known to be frequently deleted or amplified in various kinds of cancers. In this study, we investigated the role miR-30a in OS. A negative correlation between miR-30a expression and malignant grade was observed in OS cell lines. The overexpression of miR-30a reduced proliferation, migration, and invasion in 143B cells and the inhibitor of miR-30a increased proliferation, migration, and invasion in Saos2 cells. Further studies revealed that runt-related transcription factors 2 (Runx2) was a regulative target gene of miR-30a. Rescue assay significantly reversed the effects of overexpressing or inhibiting miR-30a. miR-30a also suppressed tumor formation and pulmonary metastasis in vivo. All the results suggest a critical role of miR-30a in suppressing proliferation, migration, and invasion of OS by targeting Runx2.

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Section: Discussionmentioning

confidence: 95%

MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2

et al. 2015

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“…This gene is regulated by a number of pathways such as Wnt signaling and bone morphogenetic protein (BMP) signaling [11]. Also, runx2 participates in the occurrence of many tumors [33–38]. In a previous study, Xiaodong et al proved a higher expression of runx2 gene and lower expression of sox9 gene in DDCS cell lines compared with CCS cell lines.…”

Section: Discussionmentioning

confidence: 99%

TCF-1 participates in the occurrence of dedifferentiated chondrosarcoma

Tang

Guo

et al. 2016

Tumor Biol.

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The present study demonstrated that T cell factor 1 (TCF-1) protein, a component of the canonical Wnt/β-catenin signaling pathway, can regulate the expression of runt-related transcription factor 2 (runx2) gene and Sry-related HMG box 9 (sox9) gene, which may participate in the differentiation of chondrosarcoma. Dedifferentiated chondrosarcoma (DDCS) is a special variant of conventional chondrosarcoma (CCS), associated with poor survival and high metastasis rate. However, little is known about the mechanism of its occurrence; thus, no effective treatment is available except surgery. Earlier, high expression of runx2 and low expression of sox9 were found in DDCS compared with CCS. Using Western blot to detect clinical tissue samples (including 8 CCS samples and 8 DDCS samples) and immunohistochemistry to detect 85 different-grade chondrosarcoma specimens, a high expression of TCF-1 in DDCS tissues was found compared with CCS tissues. This difference in expression was related to patients’ prognosis. Results of luciferase, chromatin immunoprecipitation, and gel electrophoresis mobility shift assays demonstrated that TCF-1 protein could bind to the promoter of runx2 gene directly and sox9 gene indirectly. Hence, it could regulate expression of runx2 gene positively and sox9 gene negatively. Furthermore, in vitro and in vivo experiments showed that TCF-1 protein was closely related to the phenotype and aggressiveness of chondrosarcoma. In conclusion, this study proved that TCF-1 participates in the dedifferentiation of DDCS, which may be mediated by runx2 gene and sox9 gene. Also, TCF-1 can be of important prognostic value and a promising therapeutic target for DDCS patients.

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“…There is also a positive correlation between the expression level of FLNBv4 and RUNX2. RUNX2 is a regulatory gene of matrix metalloproteinase 13 (MMP13) and its encoded protein, Runx2, can activate the expression of MMP13 and hence promote the osteoclast differentiation and osteolysis (27). Moreover, Runx2 contributes to the progression of cell cycle exit through binding with the hypophosphorylated form of pRb.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of filamin B splice variants in giant cell tumor cells

et al. 2016

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Giant cell tumor of bone (GCT) is the most commonly reported non-malignant bone tumor in Hong Kong. This kind of tumor usually affects people aged 20–40 years. Also, it is well known for recurrence locally, especially when the tumor cannot be removed completely. Filamins are actin-binding proteins which contain three family members, filamin A, B and C. They are the products of three different genes, FLNA, FLNB and FLNC, which can generate various transcript variants in different cell types. In this study, we focused on the effects of FLNBv2 and FLNBv4 toward GCT cells. The only difference between FLNBv2 and FLNBv4 is that FLNBv4 does not contain hinge 1 region. We found that the relative abundance of FLNBv4 varies among different GCT cell lines while the expression level of FLNBv4 in normal osteoblasts was only marginally detectable. In the functional aspect, overexpression of FLNBv4 led to upregulation of RANKL, OCN, OPG and RUNX2, which are closely related to GCT cell survival and differentiation. Moreover, FLNBv4 can have a negative effect on cell viability of GCT cells when compare with FLNBv2. In conclusion, splicing variants of FLNB are differentially expressed in GCT cells and may play a role in the proliferation and differentiation of tumor cells.

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MiR-30a inhibits osteolysis by targeting RunX2 in giant cell tumor of bone

Cited by 34 publications

References 20 publications

MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2

MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2

TCF-1 participates in the occurrence of dedifferentiated chondrosarcoma

Differential expression of filamin B splice variants in giant cell tumor cells

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