br Conflict of interest br Introduction Osteosarcoma is
Conflict of interest
Introduction Osteosarcoma is one of the most common primary bone tumor and occurs predominantly in children and young adults . With the development of multiple therapeutic strategies including wide tumor excision, neoadjuvant or adjuvant chemotherapy, and radiotherapy, the 5 year survival of the non-metastatic patients has increased to 65% . However, osteosarcoma is very aggressive and approximately 40–50% of patients will eventually develop metastases, especially pulmonary metastases . The prognosis of these patients is rather poor, and the long-term survival rate is only 10–30% . The complex molecular mechanisms underlying osteosarcoma tumorigenesis and progression remain largely unclear. Identification of new candidate molecules that take part in these processes is crucial for developing new therapeutic approach for osteosarcoma and improving clinical outcomes of patients with this disease. Long noncoding RNAs (lncRNAs) are defined as RNA transcripts of more than 200 nucleotides in length with no or little protein-coding capacity . LncRNAs can regulate gene Spadin through diverse mechanisms including epigenetic silencing, mRNA splicing, lncRNA-miRNA interaction, lncRNA-protein interaction and lncRNA-mRNA interaction . Recent studies showed that lncRNAs are involved in a wide range of biological processes, such as embryonic development, cell proliferation, apoptosis, invasion, metastasis and angiogenesis [7–9]. Furthermore, lncRNAs can act as oncogenes or tumor suppressors, and play important roles in carcinogenesis and cancer development [10,11]. Abnormal lncRNA expression and its association with various important clinicopathological parameters have been reported in many types of cancers. In terms of osteosarcoma, increased lncRNA FGFR3-AS1 expression correlated with large tumor size, advanced Enneking stage, and poor survival . Plasma lncRNA TUG1 contributed to osteosarcoma detection and dynamic surveillance . Silence of lncRNA TUSC7 promoted osteosarcoma cell proliferation and increased colony formation in vitro . LncRNA ODRUL inhibition could inhibit osteosarcoma cell proliferation and migration, and partly reversed doxorubicin resistance . Therefore, lncRNAs may be utilized for osteosarcoma diagnosis and prognosis, and serve as potential therapeutic targets. Urothelial carcinoma associated 1 (UCA1) is an lncRNA originally identified in human bladder carcinoma . Overexpression of UCA1 significantly enhanced bladder cancer cell proliferation and migration and confered drug resistance. Recently, UCA1 has been reported to be upregulated and exert its oncogenic activity in several cancers such as esophageal squamous cell carcinoma , breast cancer , non-small cell lung cancer , gastric cancer , colorectal cancer, hepatocellular carcinoma , renal cell carcinoma , ovarian cancer , and prostate cancer . However, the significance of UCA1 in osteosarcoma is still unclear. In the present study, we investigated the expression level of UCA1 in osteosarcoma samples and cell lines. We also investigated the correlation between UCA1 expression and clinicopathological characteristics and patient\'s survival. Moreover, we explored the role of UCA1 in the regulation of biological behaviors of osteosarcoma cells.
Materials and methods
Discussion It is urgent to develop novel targets for the diagnosis, treatment, and prognosis of osteosarcoma. Increasing evidence has demonstrated that lncRNAs play important roles in almost every aspects of physiological and pathological processes in the human body . Changes of lncRNA expression are involved in cancer formation and progression, which may provide a new but promising way to deal with cancer [26,27]. In the present study, we observed high UCA1 expression in osteosarcoma tissues and cell lines, providing the first evidence that UCA1 upregulation was closely associated with osteosarcoma initiation. Then we confirmed the correlation between increased UCA1 levels and aggressive clinicopathological features of osteosarcoma samples. UCA1 overexpression enhanced HOS cell proliferation, invasion and migration, and inhibited cell apoptosis, whereas UCA1 silencing in MG-63 cells showed opposite effects. These findings revealed that UCA1 might contribute to osteosarcoma progression and serve as a potential therapeutic target. Furthermore, osteosarcoma patients with high UCA1 levels tended to have shorter overall survival compared to patients with low UCA1 levels, and multivariate Cox hazard regression analysis identified UCA1 expression as an independent prognostic indicator. To our knowledge, this is the first study to analyze the expression and clinical significance of UCA1 in osteosarcoma.