OncoTargets and Therapy (Aug 2020)

lncRNA LSINCT5 Regulates miR-20a-5p/XIAP to Inhibit the Growth and Metastasis of Osteosarcoma Cells

  • Liao SA,
  • Guan J,
  • Mo H,
  • He JL,
  • Zhan XL

Journal volume & issue
Vol. Volume 13
pp. 8209 – 8221

Abstract

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Shi-An Liao,1 Jian Guan,2 Hao Mo,2 Ju-Liang He,2 Xin-Li Zhan1 1Department of Spine and Osteopathy Ward, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, People’s Republic of China; 2Department of Bone and Soft Tissue Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Province, People’s Republic of ChinaCorrespondence: Xin-Li ZhanDepartment of Spine and Osteopathy Ward, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of ChinaTel +86-13907864389Email [email protected]: More and more evidence has shown that non-coding RNA (ncRNA), including long ncRNA (lncRNA) and micro RNA (miRNA), plays a crucial regulatory role in osteosarcoma (OS). Previously, we revealed a Rho-related coiled coil incorporating protein kinase 1(XIAP). A transfer-related gene is negatively regulated by microRNA-20a-5p (miR-20a-5p) and plays the role of oncogene in OS. It is not clear if any lncRNA is involved in the axial upstream of miR-20a-5p/XIAP.Methods: Expression of LSINCT5 and miR-20a-5p/XIAP in OS tissues was determined through qRT-PCR (qP). The proliferation and migration/invasion activity of OS cells were tested through CCK-8/and transwell assay, respectively. The changes on expression of XIAP were examined through qRT-PCR and Western blot (WB). Targeted binding between LSINCT5, miR-20a-5p, and XIAP has been verified using dual luciferase reporter gene analysis, RNA Immunoprecipitation (RIP), and RNA pull-down experiments. The effect of LSINCT5 on tumor growth was determined by tumor allograft test.Results: In this study, elevated LSINCT5 was found in OS tissue samples and OS cell strains, and the increased LSINCT5 was strongly related to the adverse prognosis of clinical patients. Functional assays showed that inhibition of LSINCT5 could up-regulate miR-20a-5p-mediated OS cells proliferation and metastasis. WB analysis and qP analysis showed that LSINCT5 regulated XIAP by mediating miR-20a-5p. Further cell behavior experiments showed that LSINCT5 acted as a miR-20a-5p sponge to inhibit proliferation and metastasis caused by XIAP. Finally, the results of animal models in vivo showed that LSINCT5 could regulate the tumor growth of OS.Conclusion: LncRNA LSINCT5 acts as an oncogene and promotes XIAP mediated growth and metastasis as competitive endogenous RNA (ceRNA) in OS.Keywords: lncRNA, LSINCT5, miR-20a-5p, osteosarcoma, growth, invasion

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