LncRNA LINC00467 contributes to osteosarcoma growth and metastasis through regulating HMGA1 by directly targeting miR-217

H.-Z. Ma, J. Wang, J. Shi, W. Zhang, D.-S. Zhou

Department of Orthopedic Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. mhz7788@163.com

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• Oncology

OBJECTIVE: Osteosarcoma (OS) is a common primary bone tumor. Despite multiple treatment strategies have made great progress, the overall clinical outcome of OS patients is frustrating. Long non-coding RNA (lncRNA) LINC00467 has been reported in several cancers, while the research of the role of LINC00467 in OS is limited. The aim of this study was to figure out the potential mechanism of LINC00467 in OS.

PATIENTS AND METHODS: The expression levels of LINC00467, microRNA-217 (miR-217) and high mobility group A1 (HMGA1) were quantified by reverse transcription quantitative polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), flow cytometry and transwell assay were performed to detect cell proliferation, apoptosis, migration and invasion, respectively. The protein levels of HMGA1, B-cell lymphoma-2 (Bcl-2), Bax, Cleaved Caspase-3 (C-Caspase 3), E-cadherin, N-cadherin and vimentin were measured by Western blot assay. Online software starbase was used to predict the binding sites of miR-217. Luciferase report assay and RNA Binding Protein Immunoprecipitation (RIP) assay were carried out for detecting the interaction between miR-217 and LINC00467 or HMGA1.

RESULTS: The expression of LINC00467 and HMGA1 was increased in OS tissues and cells, while miR-217 expression was reduced. High expression of HMGA1 led to the poor overall survival. Down-regulation of LINC00467 or up-regulation of miR-217 could accelerate cell apoptosis, and slump cell proliferation, migration, invasion and EMT. However, miR-217 under-expression or HMGA1 over-expression could rescue these effects. Moreover, it was indicated that LINC00467 directly targeted miR-217 and HMGA1 was a target of miR-217.

CONCLUSIONS: LINC00467 promoted cell proliferation, migration, invasion and EMT, and suppressed cell apoptosis by up-regulating HMGA1 via targeting miR-217.

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