MiRNAs are differentially expressed in various tissues and cells, suggesting their potential applications as biomarkers and therapeutic targets [6]

MiRNAs are differentially expressed in various tissues and cells, suggesting their potential applications as biomarkers and therapeutic targets [6]. and invasion. Moreover, we identified WASF3 as a novel functional downstream target of miR-217. The ectopic expression of WASF3 can partially reverse the inhibition of cell proliferation and invasion caused by miR-217. Take together, our results demonstrate that miR-217 functions as a tumor-suppressive miRNA and inhibits the osteosarcoma tumorigenesis through targeting WASF3. Introduction Osteosarcoma is the most common type of primary sarcoma of the bone and a leading cause of cancer death in adolescents due to its rapid proliferation [1], [2]. Despite the rapid development in therapeutic strategies, such as wide tumor excision, adjuvant chemotherapy and radiotherapy, the cure rate of patients of osteosarcoma is still very low [3]. Although recent advances in molecular biology have provided some clues to the molecular pathogenesis of osteosarcoma, the exact molecular mechanisms underlying the histological heterogeneity, drug resistance, and development of metastasis remain unclear [4]. Therefore, it is urgent to develop novel targets for TBA-354 the diagnosis, treatment, and prognosis of osteosarcoma. MicroRNAs (miRNAs) are a class endogenous small non-coding RNAs that regulate gene expression by the inhibition of the translation and/or decreasing of the stability of target mRNAs [5]. MiRNAs are differentially expressed in various tissues and cells, suggesting their potential applications as biomarkers and therapeutic targets [6]. MiRNAs are deregulated in several diseases including cancers, where they play important roles by regulating the expression of various tumor oncogenes and suppressors [7], [8]. MiRNAs also can act as oncogenes or tumor suppressors and involve in numerous cellular processes, playing roles in tumorigenesi by regulating cell differentiation, cell proliferation and cell cycle [9]C[13]. However, the role of miRNAs in osteosarcoma tumor development and metastasis has only recently been investigated and remains largely unknown. Previous studies have U2AF1 showed that miR-217 was a novel tumor biomarker of clear cell TBA-354 renal cell carcinoma [14]. It could target oncogenes or tumor suppressor genes in different cell type. For example, miR-217 could target KRAS, previously shown to function as a tumor suppressor by inhibiting tumor cell growth and anchorage-independent colony formation [15]. MiR-217 could also act as oncogene by targeting the tumor suppressor gene PTEN in kidney disorders [16]. In addition, miR-217 could target silent information regulator 1 (SirT1), and function as an oncogene [17]. However, no specific study has been showed to investigate the role of miR-217 in osteosarcoma. In this report, we investigated the role of miR-217 in human osteosarcoma. First, we investigated the expression of miR-217 in human osteosarcoma cell lines and tissues, and paired adjacent non-tumor bone tissue. Second, we examined the cell growth, migration, and invasion following overexpression or downregulation of miR-217 in osteosarcoma cell lines. Finally, we determined the target gene of miR-217 using the luciferase reporter assay and western blot. Materials and Methods Ethics Statement All of these patients or TBA-354 patients’ parents on behalf of the children agreed to participate in the study and gave written informed consent. TBA-354 Both this study and consent were approved by the ethical board of the institute of The First Affiliated Hospital of Jiamusi University and complied with the Declaration of Helsinki. Tissue samples Surgically resected 60 osteosarcomas specimens and their morphologically normal bone tissues (before the administration of neoadjuvant chemotherapy) were acquired from The First Affiliated Hospital of Jiamusi University between November 2007 and November 2013. Tissue samples were cut into two parts and one part was fixed with 10% formalin for histopathological diagnosis. The other was immediately snap-frozen in liquid nitrogen and then stored at ?196C in liquid nitrogen until it was needed for RNA was extracted. The use of tissue samples for all of these experiments was approved by the patients and by the Ethics Committee of the institution. These patient characteristics were described in Table S1..