LncSNHG16 promotes proliferation and migration of osteosarcoma cells by targeting microRNA-146a-5p

S.-N. Zheng, D.-W. Ge, J. Tang, J. Yang, J.-W. Yan, J.-J. Qiu, Z.-W. Yin, Y. Ni, L. Zhao, X. Chen, L. Yang

Department of Orthopedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. leiyang@njmu.edu.cn

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• Oncology

OBJECTIVE: The aim of this study was to elucidate the regulatory role of lncSNHG16 in the progression of osteosarcoma (OS) and its underlying mechanism.

MATERIALS AND METHODS: Expressions of lncSNHG16, microRNA-146a-5p and NOVA1 in OS tissues and adjacent normal tissues were determined by quantitative Real-time polymerase chain reaction (qRT-PCR). Their expressions in OS cell lines were detected by qRT-PCR as well. We analyzed the relationship between lncSNHG16 expression and tumor stage, diagnosis and survival prognosis of OS patients, respectively. Cell counting kit-8 (CCK-8) and transwell experiments were conducted to explore proliferative and migratory changes of OS cells. Dual-luciferase reporter assay was used to verify the binding relationship of lncSNHG16 to microRNA-146a-5p, and microRNA-146a-5p to NOVA1. Finally, rescue experiments were performed to elucidate the regulatory effect of lncSNHG16 on the cellular behaviors of OS cells.

RESULTS: LncSNHG16 was highly expressed in OS tissues and cell lines. Its expression was positively correlated with the tumor stage of OS patients. Receiver operating characteristic (ROC) curves suggested that lncSNHG16 can be used as a clinical indicator to distinguish OS patients from healthy controls. Survival analysis indicated a negative correlation between lncSNHG16 expression and survival of OS patients. Overexpression of lncSNHG16 enhanced the proliferative and migratory potentials of OS cell lines 143B and MNNG/HOS. MicroRNA-146a-5p was predicted to be the target gene of lncSNHG16, which was lowly expressed in OS tissues and cell lines. Overexpression of lncSNHG16 downregulated the expression of microRNA-146a-5p in 143B and MNNG/HOS cells. Furthermore, we verified that lncSNHG16 could bind to microRNA-146a-5p. The promotive role of lncSNHG16 in proliferative and migratory potentials of OS cells was reversed by microRNA-146a-5p. Subsequently, NOVA1 was predicted to be the target gene of microRNA-146a-5p, and was further verified by dual-luciferase reporter gene assay. Correlation analysis showed that microRNA-146a-5p expression was negatively correlated with NOVA1 expression in OS. More importantly, NOVA1 reversed the inhibitory effect of microRNA-146a-5p on the proliferative and migratory capacities of 143B and MNNG/HOS cells.

CONCLUSIONS: LncSNHG16 is highly expressed in OS tissues and cell lines, participating in the development of OS by downregulating microRNA-146a-5p to upregulate NOVA1 expression.

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