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MiR-16-1-3p and miR-16-2-3p Possess Strong Tumor Suppressive and Antimetastatic Properties in Osteosarcoma

MiR-16-1-3p and miR-16-2-3p Possess Strong Tumor Suppressive and Antimetastatic Properties in Osteosarcoma

Vadim V Maximov, Rania Akkawi, Saleh Khawaled, Zaidoun Salah, Lina Jaber, Ahlam Barhoum, Omer Or, Marco Galasso, Kyle C Kurek, Eylon Yavin, Rami I Aqeilan

Int J Cancer. 2019 Dec 1;145(11):3052-3063.

PMID: 31018244

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42410498	17α-Hydroxypregnenolone-20,21-13C2,16,16-d2			Price

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