Abstract
Recent studies have revealed that long noncoding RNA HNF1A‐antisense 1 (HNF1A‐AS1) plays an important role in the development of several human malignancy entities. However, the expression and function of HNF1A‐AS1 in the carcinogenesis and development of osteosarcoma remains unknown. In this study, we detected the HNF1A‐AS1 levels in human osteosarcoma tissues and cell lines by quantitative real‐time polymerase chain reaction (qRT‐PCR), and investigated its role in osteosarcoma by using in vitro assays. Our study showed that HNF1A‐AS1 expression was significantly up‐regulated in human osteosarcoma tissues and cell lines compared with their normal counterparts, and its expression level was positively correlated with the distance metastasis (P = 0.009) and tumour stage (P = 0.019). Moreover, Kaplan–Meier curves with the log‐rank test showed that higher expression of HNF1A‐AS1 conferred a significantly poorer survival and multivariate Cox proportional hazards analysis revealed that HNF1A‐AS1 was an independent risk factor of overall survival. In addition, the expression of HNF1A‐AS1 in serum is correlated with patients’ status and receiver operating characteristic (ROC) curve analysis demonstrated that HNF1A‐AS1 could distinguish patients with osteosarcoma from healthy individuals (the area under curve 0.849, P < 0.001). Furthermore, in vitro knockdown of HNF1A‐AS1 by siRNA significantly inhibited cell proliferation and G1/S transition, and suppressed migration and invasion by reducing the epithelial‐mesenchymal transition (EMT) program in osteosarcoma cells. Taken together, our data suggested that HNF1A‐AS1 is a novel molecule involved in osteosarcoma progression, which may provide as a potential diagnostic, prognostic biomarker and therapeutic target.
Highlights
Osteosarcoma is one of the most common type of primary sarcoma of the bone cancer in orthopaedics [1, 2]
Our results showed that HNF1A-AS1 expression in human osteosarcoma tissues was significantly higher than that in adjacent non-tumour tissues (Fig. 1A, P = 0.018)
Based on the expression levels of HNF1A-AS1 obtained by qRT– PCR, we divided the 72 osteosarcoma patients into a high-HNF1AAS1 expression group and a low-HNF1A-AS1 expression group
Summary
Osteosarcoma is one of the most common type of primary sarcoma of the bone cancer in orthopaedics [1, 2]. Wide tumour excision is effective on primary disease, in addition to currently widely adopted adjuvant chemotherapy and radiotherapy on metastatic lesions, the cure rate of osteosarcoma patients remain dismal [3, 4]. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. Understanding the exact molecular mechanisms underlying the histological heterogeneity, development of metastasis and drug resistance is essential for illustrating the molecular pathogenesis of osteosarcoma, as well as developing novel targets for the diagnosis, prognosis and treatment of osteosarcoma.
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