PT - JOURNAL ARTICLE AU - Vadim V. Maximov AU - Saleh Khawaled AU - Zaidoun Salah AU - Lina Jaber AU - Nataly Bengaiev AU - Ahlam Barhoum AU - Marco Galasso AU - Eylon Yavin AU - Rami I. Aqeilan TI - MiR-16-1<sup>*</sup> and miR-16-2<sup>*</sup> possess strong tumor suppressive and anti-metastatic properties in osteosarcoma AID - 10.1101/412411 DP - 2018 Jan 01 TA - bioRxiv PG - 412411 4099 - http://biorxiv.org/content/early/2018/09/09/412411.short 4100 - http://biorxiv.org/content/early/2018/09/09/412411.full AB - 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* and miR-16-2* “passenger” strands as well as the “lead” miR-16 strand possess strong tumor suppressive functions in human OS. We report different although strongly overlapping functions for miR-16-1* and miR-16-2* 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* and miR-16-2* in OS cells. Furthermore, validation experiments identified FGFR2 as a direct target for miR-16-1* and miR-16-2*. Overall, our findings underscore the importance of passenger strand miRNAs in osteosarcomagenesis.Novelty and Impact Osteosarcoma (OS) can be a fatal disease. MicroRNAs (miRNAs) play crucial roles in osteosarcomagenesis. In this study, we identify miR-16-1* and miR-16-2* as strong tumor suppressors and anti-metastatic genes in OS. This is the first report demonstrating tumor suppressive functions of passenger strands of these miRNAs in OS. Given that MIR-16-1 is located in 13q14 region that is commonly deleted in several human malignancies, our findings shed light on oncogenic mechanisms triggered by 13q14 deletion.AbbreviationsOSosteosarcomamiRISCmicroRNA-induced silencing complexmRNAmessenger RNACLLchronic lymphocytic leukemiaRIPRNA Immunoprecipitation