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Deregulated miRNAs in osteoporosis: effects in bone metastasis

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Abstract

Starting from their role exerted on osteoblast and osteoclast differentiation and activity pathways, microRNAs (miRNAs) have been recently identified as regulators of different processes in bone homeostasis. For this purpose, in a recent review, we highlighted, as deregulated miRNAs could be involved in different bone diseases such as osteoporosis. In addition, recent studies supported the concept that osteoporosis-induced bone alterations might offer a receptive site for cancer cells to form bone metastases, However, to date, no data on specific-shared miRNAs between osteoporosis and bone metastases have been considered and described to clarify the evidence of this link. The main goal of this review is to underline as deregulated miRNAs in osteoporosis may have specific roles in the development of bone metastases. The review showed that several circulating osteoporotic miRNAs could facilitate tumor progression and bone-metastasis formation in several tumor types, i.e., breast cancer, prostate cancer, non-small-cell lung cancer, esophageal squamous cell carcinoma, and multiple myeloma. In detail, serum up-regulation of pro-osteoporotic miRNAs, as well as serum down-regulation of anti-osteoporotic miRNAs are common features of all these tumors and are able to promote bone metastasis. These results are of key importance and could help researcher and clinicians to establish new therapeutic strategies connected with deregulation of circulating miRNAs and able to interfere with pathogenic processes of osteoporosis, tumor progressions, and bone-metastasis formation.

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Abbreviations

3′UTR:

3′ Untranslated region

AGO2:

Argonaut 2

BC:

Breast cancer

BMSCs:

Bone-marrow mesenchymal stem cells

BMPs:

Bone morphogenetic proteins

CNTF:

Ciliary neurotrophic factor

DGCR8:

Di George syndrome critical region gene 8

ESCC:

Esophageal squamous cell carcinoma

GPC3:

Glypican 3

IL:

Interleukin

MM:

Multiple myeloma

MMP:

Matrix metalloproteinase

MTSS1:

Metastasis suppressor protein 1

MiRNAs:

MicroRNAs

NSCLC:

Non-small-cell lung cancer

OB:

Osteoblast

OC:

Osteoclast

OPG:

Osteoprotegerin

PC:

Prostate cancer

PTH:

Parathyroid hormone

PBMCs:

Peripheral blood mononuclear cells

qRT-PCR:

Quantitative real-time polymerase chain reaction

RANKL:

Receptor activator of nuclear factor kappa-B ligand

SREs:

Skeletal-related events

TGFβ:

Transforming growth factor-beta

TNFα:

Tumor necrosis factor alpha

Wnt:

Wingless-type MMTV integration site family

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Acknowledgements

Dr. Daniele Bellavia, Dr. Angela De Luca, Dr. Valeria Carina, Dr. Viviana Costa, and Dr. Lavinia Raimondi contributed to the manuscript by working at the Technology Platform of Tissue Engineering, Theranostics and Oncology (Lab.Manager Dr. Gianluca Giavaresi), a laboratory started-up by the Rizzoli Orthopedic Institute in Palermo (Italy) with the grants also of National Operative Program projects (PON, MIUR).

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Authors and Affiliations

  1. IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

    Daniele Bellavia, L. Raimondi, A. De Luca, V. Carina & V. Costa

  2. Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

    F. Salamanna, M. Fini & G. Giavaresi

  3. Section of Biology and Genetics, Department of BioMedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), University of Palermo, 90133, Palermo, Italy

    R. Alessandro

  4. Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, Palermo, Italy

    R. Alessandro

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  1. Daniele Bellavia
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  2. F. Salamanna
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Correspondence to Daniele Bellavia.

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Bellavia, D., Salamanna, F., Raimondi, L. et al. Deregulated miRNAs in osteoporosis: effects in bone metastasis. Cell. Mol. Life Sci. 76, 3723–3744 (2019). https://doi.org/10.1007/s00018-019-03162-w

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