Upregulation of microRNA-17-92 cluster associates with tumor progression and prognosis in osteosarcoma

Abstract

MicroRNA -17-92 (miR-17-92) cluster has been demonstrated to play a crucial role in various human cancers. However, its effects in osteosarcoma have not yet been elucidated. The purpose of this study was to investigate the clinical significance of miR-17-92 cluster in osteosarcoma. MiR-17-92 cluster expression in osteosarcoma clinical samples and cell lines was detected by real-time quantitative RT-PCR. Then, the association of miR-17-92 cluster level with survival of osteosarcoma patients was performed by the Kaplan-Meier and Cox proportional regression analyses. Furthermore, the effects of miR-17-92 cluster on tumorigenicity of osteosarcoma cell lines were evaluated by in vitro assays. The relative expression of miR-17-92 cluster in osteosarcoma tissues was significantly higher than those in adjacent normal tissues (P=0.001). And there was a relationship between miR-17-92 cluster upregulation and advanced TNM stage of osteosarcoma patients (P=0.037). Moreover, higher miR-17-92 cluster expression clearly predicted poorer Recurrence-free survival (P<0.001) and Overall survival (P=0.002). In the multivariate analysis, high miR-17-92 cluster expression was an independent prognostic factor for Recurrence-free survival (P<0.001) and Overall survival (P=0.002). Furthermore, the cellular proliferation, invasion, and migration of osteosarcoma cell lines were significantly accelerated by miR-17-92 cluster plasmid in vitro assays. Our findings showed that miR-17-92 cluster could serve as a promising marker for tumor recurrence and survival of osteosarcoma patients. Moreover, miR-17-92 cluster has been identified as a promoter for tumorigenicity of osteosarcoma cells, thus it might be a critical targeted therapy strategy for osteosarcoma.

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

“…Among the target miRNAs, miR-18a-5p was selected as the study object, based on its biological function in various cancers [19,20]. miR-18a-5p, Cellular Physiology and Biochemistry a member of the miR-17-92 cluster, has been reported to be upregulated, and functions as an oncogene in OS progression [25][26][27]. We further confirmed by luciferase reporter assay and qRT-PCR, that FER1L4 interacts directly with miR-18a-5p, both in OS cell lines as well as in tissues.…”

Serum microRNA-17 functions as a prognostic biomarker in osteosarcoma

“…Previous studies demonstrated that PTEN is a target gene of miR-17 and its expression appears to be inversely correlated with miR-17 expression levels in OS tissues (27,28). In the present study, PTEN expression was significantly decreased in human OS tissues compared with in matched normal tissues (P<0.01), indicating that downregulation of PTEN may have a significant role in OS development and progression (Fig.…”

Alterative Expression and Localization of Profilin 1/VASPpS157 and Cofilin 1/VASPpS239 Regulates Metastatic Growth and Is Modified by DHA Supplementation

“…DHA supplementation has been previously shown to inhibit cancer cell adhesion, proliferation and invasiveness (38, 40). We propose the basic concept that in cancer cells, disease progression involves changes in actin binding protein-mediated actin dynamic which facilitates metastasis and increases cell survival.…”

“…MiR-17~92, a cluster of six microRNAs encoded by a single transcript, is highly expressed in malignant tumors and may function as an oncogene by negatively regulating tumor suppressor genes and/or genes that control cell proliferation, differentiation, or apoptosis (36–38). Of relevance, ABPs like profilin 1 and cofilin 1 are among the predicted targets of miR~17–92 (predicted by Target Scan).…”