The lncRNA HNF1A‐AS1 is a negative prognostic factor and promotes tumorigenesis in osteosarcoma

• Published in: Journal of cellular and molecular medicine Vol. 21; no. 11; pp. 2654 - 2662
• Main Authors: Cai, Lijun, Lv, Jinhan, Zhang, Yinquan, Li, Junhong, Wang, Yinong, Yang, Huilin
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.11.2017
• Subjects: Adult; Area Under Curve; biomarker; Bone Neoplasms - blood; Bone Neoplasms - diagnosis; Bone Neoplasms - genetics; Bone Neoplasms - mortality; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogenesis - pathology; Cell Line, Tumor; Cell Proliferation; Disease Progression; Epithelial-Mesenchymal Transition; Female; function; G1 Phase Cell Cycle Checkpoints - genetics; Gene Expression Regulation, Neoplastic; HNF1A‐AS1; Humans; long noncoding RNA; Male; Middle Aged; Original; osteosarcoma; Osteosarcoma - blood; Osteosarcoma - diagnosis; Osteosarcoma - genetics; Osteosarcoma - mortality; Prognosis; Proportional Hazards Models; Risk Factors; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - blood; RNA, Long Noncoding - genetics; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; ROC Curve; long noncoding RNA; biomarker; osteosarcoma; HNF1A-AS1; function
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12944

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.