MicroRNAs in the control of metastatic bone disease

Browne, Gillian; Taipaleenmäki, Hanna; Stein, Gary S.; Lian, Jane B.

doi:10.1016/j.tem.2014.03.014

Cited by 62 publications

(62 citation statements)

References 98 publications

(86 reference statements)

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“…MiRNAs are key regulators of various biological processes including bone homeostasis and bone pathologies (14, 15, 17), cancer progression and metastasis (18, 19). Therefore in vivo delivery of miRNAs or miRNA antagonists provides an attractive therapeutic tool to reverse bone tissue degeneration (16), or to prevent cancer-induced bone diseases (20).…”

Section: Introductionmentioning

confidence: 99%

Targeting of Runx2 by miR-135 and miR-203 Impairs Progression of Breast Cancer and Metastatic Bone Disease

et al. 2015

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Progression of breast cancer to metastatic bone disease is linked to deregulated expression of the transcription factor Runx2. Therefore, our goal was to evaluate the potential for clinical use of Runx2-targeting microRNAs (miRNAs) to reduce tumor growth and bone metastatic burden. Expression analysis of a panel of miRNAs regulating Runx2 revealed a reciprocal relationship between the abundance of Runx2 protein and two miRNAs, miR-135 and miR-203. These miRNAs are highly expressed in normal breast epithelial cells where Runx2 is not detected, and absent in metastatic breast cancer cells and tissue biopsies that express Runx2. Reconstituting metastatic MDA-MB-231-Luc cells with miR-135 and miR-203 reduced the abundance of Runx2 and expression of the metastasis-promoting Runx2 target genes IL-11, MMP-13, and PTHrP. Additionally, tumor cell viability was decreased and migration suppressed in vitro. Orthotopic implantation of MDA-MB-231-luc cells delivered with miR-135 or miR-203, followed by an intratumoral administration of the synthetic miRNAs reduced the tumor growth and spontaneous metastasis to bone. Furthermore, intratibial injection of these miRNA-delivered cells impaired tumor growth in the bone environment and inhibited bone resorption. Importantly, reconstitution of Runx2 in MDA-MB-231-luc cells delivered with miR-135 and miR-203 reversed the inhibitory effect of the miRNAs on tumor growth and metastasis. Thus, we have identified that aberrant expression of Runx2 in aggressive tumor cells is related to the loss of specific Runx2-targeting miRNAs and that a clinically relevant replacement strategy by delivery of synthetic miRNAs is a candidate therapeutic approach to prevent metastatic bone disease by this route.

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Section: Introductionmentioning

confidence: 99%

Targeting of Runx2 by miR-135 and miR-203 Impairs Progression of Breast Cancer and Metastatic Bone Disease

et al. 2015

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“…Previous studies have demonstrated that miRNAs played an important role in the development of osteoporosis [11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1

Yang

Ge²,

Cao³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Postmenopausal osteoporosis is closely associated with reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Previous studies have demonstrated that miR-214 plays an important role in the genesis and development of postmenopausal osteoporosis. Here, we performed this study to investigate the potential mechanism by which miR-214 regulates osteoblast differentiation of MSCs. Methods: First, we explored the expression of miR-214 in MSCs of osteoporotic mice. Next, we examined the change of miR-214 during osteoblast differentiation of MSCs. Then, MSCs were infected with lentiviral vectors expressing miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of MSCs. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-214. Results: MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that FGFR1 is a direct target of miR-214. Conclusions: MiR-214 attenuates osteogenesis by inhibiting the FGFR1/FGF signaling pathway. Our findings suggest that targeting miR-214 promises to be a potential therapy in treatment of postmenopausal osteoporosis.L. Yang and D. Ge contributed to the work equally.

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“…Indeed, it has recently been shown that, in acute myeloid leukaemia, this mechanism involves vesicle-based trafficking of miRs from cancer cells to the bone during metastasis and that secreted miRs have functional affects upon the bone niche 53. Additionally, the role of miRs in regulating the interaction of PCa cells and the bone metastatic niche is well acknowledged (reviewed in refs 54 and 55). The identification of stem cell specific mechanisms, and of miR mechanisms particularly, may facilitate future targeting of the bone metastatic niche in a similar fashion.…”

Section: Discussionmentioning

confidence: 99%

Enhanced regulation of cell cycle and suppression of osteoblast differentiation molecular signatures by prostate cancer stem-like holoclones

et al. 2015

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MicroRNAs in the control of metastatic bone disease

Cited by 62 publications

References 98 publications

Targeting of Runx2 by miR-135 and miR-203 Impairs Progression of Breast Cancer and Metastatic Bone Disease

Targeting of Runx2 by miR-135 and miR-203 Impairs Progression of Breast Cancer and Metastatic Bone Disease

MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1

Enhanced regulation of cell cycle and suppression of osteoblast differentiation molecular signatures by prostate cancer stem-like holoclones

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