• Clinics · Jan 2023

    LncRNA ZFAS1 contributes to osteosarcoma progression via miR-520b and miR-520e-mediated inhibition of RHOC signaling.

    • Xiaofeng Liu, Mingyang Wang, Liwen Zhang, and Lei Huang.
    • Department of Orthopaedics, The First Affiliated Hospital of Dalian Medical University, Liaoning, People's Republic of China.
    • Clinics (Sao Paulo). 2023 Jan 1; 78: 100143100143.

    ObjectivesWe examined the expression of Lnc-ZFAS1 in osteosarcoma and comprehensively evaluated its effects on osteosarcoma in vitro and vivo. Moreover, we revealed the regulatory mechanism between Lnc-ZFAS1 and miR-520b/miR-520e-mediated RHOC and provided a novel clue for ameliorating osteosarcoma.MethodThe expression of Long non-coding RNA Zinc Finger Antisense 1 (LncRNA ZFAS1) osteosarcoma tissues and normal tissues in the TCGA database was analyzed. Then, LncRNA ZFAS1 expression was further verified in clinical samples and osteosarcoma cell lines (U2OS and KHOS), as well as the human osteoblast cell line hFOB1.19 by qRT-PCR. Thereafter, LncRNA ZFAS1 was overexpressed or silenced to explore its effects on cell proliferation, apoptosis, migration, invasion, and Epithelial-Mesenchymal Transition (EMT). The fundamental mechanism through which Lnc-ZFAS1 affects osteosarcoma progression was further investigated and verified.ResultsWe found that LncRNA ZFAS1 was upregulated in osteosarcoma, and Lnc-ZFAS1 overexpression facilitated osteosarcoma cells proliferation, migration, invasion and EMT, while Lnc-ZFAS1 silence exerted reverse influence. Mechanistically, Lnc-ZFAS1 functionally acted as a sponger of microRNA-520b (miR-520b) and microRNA-520e (miR-520e) to up-regulate Ras Homologue C (RHOC). In addition, depleted Lnc-ZFAS1 restrained osteosarcoma cells proliferation, migration, and invasion, which could be rescued by RHOC overexpression. Lnc-ZFAS1 was upregulated in osteosarcoma and Lnc-ZFAS1 could exert promoted impact upon osteosarcoma cells proliferation, migration, invasion, and EMT in vitro.ConclusionsLnc-ZFAS1 acted sponger of miR-520b and miR-520e to promote RHOC, indicating that Lnc-ZFAS1/miR-520b/RHOC and Lnc-ZFAS1/miR-520e/RHOC axes might serve as potential therapeutic strategies against osteosarcoma.Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.

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