MiR-16-1-3p and miR-16-2-3p possess strong tumor suppressive and antimetastatic properties in osteosarcoma.
Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation
Down-Regulation
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ genetics
Mice
MicroRNAs
/ genetics
Neoplasm Transplantation
Osteonecrosis
/ genetics
Osteosarcoma
/ genetics
Receptor, Fibroblast Growth Factor, Type 2
/ genetics
FGFR2
RIP
metastasis
miR-16-1
miR-16-2
miR-16-5p
osteosarcoma
tumor suppressor
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
received:
04
11
2018
revised:
18
03
2019
accepted:
10
04
2019
pubmed:
25
4
2019
medline:
1
2
2020
entrez:
25
4
2019
Statut:
ppublish
Résumé
Osteosarcoma (OS) is an aggressive malignancy affecting mostly children and adolescents. MicroRNAs (miRNAs) play important roles in OS development and progression. Here we found that miR-16-1-3p and miR-16-2-3p "passenger" strands, as well as the "lead" miR-16-5p strand, are frequently downregulated and possess strong tumor suppressive functions in human OS. Furthermore, we report different although strongly overlapping functions for miR-16-1-3p and miR-16-2-3p in OS cells. Ectopic expression of these miRNAs affected primary tumor growth, metastasis seeding and chemoresistance and invasiveness of human OS cells. Loss-of-function experiments verified tumor suppressive functions of these miRNAs at endogenous levels of expression. Using RNA immunoprecipitation (RIP) assays, we identify direct targets of miR-16-1-3p and miR-16-2-3p in OS cells. Moreover, validation experiments identified FGFR2 as a direct target for miR-16-1-3p and miR-16-2-3p. Overall, our findings underscore the importance of passenger strand miRNAs, at least some, in osteosarcomagenesis.
Substances chimiques
MIRN16 microRNA, human
0
MicroRNAs
0
FGFR2 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3052-3063Informations de copyright
© 2019 UICC.
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