The miR-143/145 Cluster, a Novel Diagnostic Biomarker in Chondrosarcoma, Acts as a Tumor Suppressor and Directly Inhibits Fascin-1.
BIOMARKER
BONE CANCER
CHONDROSARCOMA
MICRORNA
TUMOR SUPPRESSOR
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
08
10
2019
revised:
24
01
2020
accepted:
29
01
2020
pubmed:
7
2
2020
medline:
29
7
2021
entrez:
7
2
2020
Statut:
ppublish
Résumé
Chondrosarcoma is the second most frequent bone sarcoma. Due to the inherent chemotherapy and radiotherapy resistance and absence of known therapeutic targets, clinical management is limited to surgical resection. Consequently, patients with advanced disease face a poor prognosis. Hence, elucidating regulatory networks governing chondrosarcoma pathogenesis is vital for development of effective therapeutic strategies. Here, miRNA and mRNA next generation sequencing of different subtypes of human chondrogenic tumors in combination with in silico bioinformatics tools were performed with the aim to identify key molecular factors. We identified miR-143/145 cluster levels to inversely correlate with tumor grade. This deregulation was echoed in the miRNA plasma levels of patients and we provided the first evidence that circulating miR-145 is a potential noninvasive diagnostic biomarker and can be valuable as an indicator to improve the currently challenging diagnosis of cartilaginous bone tumors. Additionally, artificial upregulation of both miRNAs impelled a potent tumor suppressor effect in vitro and in vivo in an orthotopic xenograft mouse model. A combined in silico/sequencing approach revealed FSCN1 as a direct target of miR-143/145, and its depletion phenotypically resembled miR-143/145 upregulation in vitro. Last, FSCN1 is a malignancy-promoting factor associated with aggressive chondrosarcoma progression. Our findings underscore miR-143/145/FSCN1 as important players in chondrosarcoma and may potentially open new avenues for specific therapeutic intervention options. © 2020 American Society for Bone and Mineral Research.
Substances chimiques
Biomarkers
0
Carrier Proteins
0
FSCN1 protein, human
0
MIRN143 microRNA, human
0
MIRN145 microRNA, human
0
MicroRNAs
0
Microfilament Proteins
0
fascin
146808-54-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1077-1091Informations de copyright
© 2020 American Society for Bone and Mineral Research.
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