Abstract. Accumulating evidence indicates that microRNAs are involved in multiple processes in cancer development and progression. microRNA-26a (miR-26a) has been identified as a tumor suppressor and its downregulation is associated with poor prognosis in several types of human cancer. However, the specific function of miR-26a in osteosarcoma remains unclear.In the present study, we found that the expression of miR-26a in osteosarcoma tissues and cell lines was much lower than that in the normal controls, respectively. In addition, downregulation of miR-26a more frequently occurred in osteosarcoma specimens with adverse clinical stage and with the presence of distant metastasis. Moreover, multivariate survival analyses demonstrated that loss of miR-26a is an independent prognostic factor for both disease-free and overall survival in osteosarcoma. In addition, restoration of miR-26a expression inhibited the invasion and migration in osteosarcoma cells, and miR-26a directly inhibited enhancer of zeste homolog 2 (EZH2) expression by targeting its 3'-UTR. Moreover, EZH2 was upregulated and inversely correlated with miR-26a expression in the osteosarcoma tissues. Thus, for the first time, we provide convincing evidence that downregulation of miR-26a is associated with tumor aggressiveness and tumor metastasis, and miR-26a inhibits cell migration and invasion by targeting the EZH2 gene in osteosarcoma. Thus, miR-26a is an independent prognostic marker for osteosarcoma patients. IntroductionOsteosarcoma, mainly arising from the metaphysis of the long bones, is the most common primary malignancy of bone in adolescents and young adults, with an estimated worldwide yearly incidence rate of 4 million (1,2). Despite current therapeutic strategies combining adjuvant chemotherapy, surgery and sometimes radiotherapy, the prognosis of osteosarcoma patients remains poor, since ~80% of patients eventually develop recurrent metastatic osteosarcoma following surgical treatment (3), and the 5-year survival rate of these patients is only 50-60% (4). Although recent developments in molecular biology have provided insight into the molecular mechanisms of osteosarcoma, the fundamental molecular mechanisms underlying metastasis in osteosarcoma have not been fully elucidated. Therefore, it is essential to identify metastasisassociated molecules as effective drug targets and to enhance the understanding of the mechanisms underlying the metastasis of osteosarcoma.MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides in length, transcribed from non-proteincoding genes or introns, which regulate gene expression through repressing translation and cleaving their target mRNAs by binding to complementary sites in their 3'-untranslated region (3'-UTR). It has been demonstrated that aberrant expression of miRNAs cause them to function as tumor suppressors or oncogenes according to the roles of their target genes (5,6). Particularly, miRNAs can regulate various cellular processes of tumor cells, including differentiation, progression, apopt...
The specific pathogenesis of steroid‑induced osteonecrosis (ON) is yet to be elucidated and until recently effective prophylactic therapies have not been available. The local renin‑angiotensin system (RAS) exists in the bone and has an important role in local bone regulation. However, to the best of our knowledge, the interrelation between local bone RAS and steroid‑induced ON is yet to be investigated. In the present study, 45 rabbits were injected with a single intramuscular dose of 20 mg/kg methylprednisolone acetate (MPA) and were sacrificed 1 (group A), 2 (group B) and 3 (group C) weeks subsequent to MPA administration (n=15 per group). Ten rabbits were used as a control group (group N). The presence or absence of ON in the bilateral femoral heads was examined histopathologically. The mRNA and protein expression of components of the RAS, including angiotensin II (Ang II), angiotensin converting enzyme (ACE) and Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors, were detected in the bone. Significant changes in Ang II, ACE, and AT1 and AT2 receptor expression were observed in the bone of the rabbits in the different groups. Moreover, the expression of Ang II and ACE was highest one week subsequent to administration of the glucocorticoid methylprednisolone and the expression of the AT1 and AT2 receptors was highest two weeks following methylprednisolone administration. ON occurs most significantly at three weeks following the administration of MPA in this animal model, thus the changes in Ang II, ACE and AT1 and AT2 receptor expression preceded this. The present study found that ON was strongly associated with the activation of the local bone RAS in rabbits.
In this study, we investigated the expression, correlation to clinical outcomes and biological functions of microRNA-15a-3p (miR-15a-3p) in human osteosarcoma.MiR-15a-3p expressions in osteosarcoma cell lines and clinical tissues of osteosarcoma patients were measured by qPCR. Relevance of endogenous miR15a-3p to osteosarcoma patients' clinicopathological factors or overall survival was statistically analyzed. In addition, the independence of miR-15a-3p predicting cancer patients' overall survival was analyzed by Cox regression method. Furthermore, in osteosarcoma cell lines, Saos-2 and HOS cells, miR-15a-3p was overexpressed through stable lentiviral transduction. The functional regulations of miR-15a-3p overexpression on cancer ell proliferation and migration were then analyzed. MiR15a-3p was significantly downregulated in osteosarcoma cell lines and human osteosarcoma tumors. Downregulation of endogenous miR-15a-3p in osteosarcoma tumors was significantly associated with cancer patient's poor clinical outcomes and low survival rate. Also, endogenous miR-15a-3p was confirmed to be an independent biomarker for predicating cancer patients' survival. In Saos-2 and HOS cells, lentivirus-induced miR-15a-3p overexpression had significantly tumor suppressing functions, by inhibiting both proliferation and migration. Significant downregulation of miR-15a-3p in osteosarcoma may be an independent biomarker to predicting cancer patients' poor prognosis. Overexpression miR-15a-3p may be an efficient functional meaning to suppress osteosarcoma development.
The estimated number of new cases of colorectal cancer (CRC) will increase to 140 250 in 2018 worldwide.The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has recently been shown to be dysregulated in CRC, which plays an important role in the progression of CRC. However, the biological role and the underling mechanism of UCA1 in the carcinogenesis of CRC remain unclear. Herein, we found that UCA1 was aberrantly upregulated in two CRC cell lines (SW620 and HT29) compared to colorectal cell CCD-18Co. UCA1 knockdown inhibited the apoptosis, growth and autophagy of CRC cell lines in vitro. Furthermore, UCA1 could act as an endogenous sponge by directly interacting with miR-185-5p and downregulation miR-185-5p expression. In addition, UCA1 could reverse the inhibitory effect of miR-185-5p on the growth and autophagy of CRC cells, which might be involved in the derepression of member 1 (WNT1)-inducible signaling pathway protein 2 (WISP2, a target gene of miR-185-5p) expression and the activation of the WISP2/b-catenin signaling pathway. In vivo, the present study elucidates a novel UCA1-miR-185-5p-WISP2-Wnt/b-catenin axis in CRC, which may help us to understand the pathogenesis and the feasibility of lncRNA-directed diagnosis and therapy of CRC. Materials and methods Cell cultureNormal colorectal cell CCD-18Co, normal epithelial cell HIEC-6, CRC-derived cells SW620 and HT29 were purchased from ATCC (Manassas, VA, USA). Cells were cultured in RPMI1640 (HyClone, UT, USA) or DMEM (HyClone) which was supplemented with 10% FBS (Gibco, NY, USA), 100 U ml À1 penicillin/streptomycin (HyClone) at 37 C in a humidied incubator with 5% CO 2 . Reagents and transfectionsThe miR-185 inhibitor, sh-UCA1, and sh-UCA1 control sequences were purchased from the GenePharma Company
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