Knockdown of the oncogene lncRNA NEAT1 restores the availability of <i>miR-34c</i> and improves the sensitivity to cisplatin in osteosarcoma

Abstract

Aberrant expressions of long non-coding RNAs (lncRNAs) are the culprits of carcinogenesis via regulating the tumor suppressor or oncogene. LncRNA nuclear enriched abundant transcript 1 (NEAT1) has been identified to be an oncogene to promote tumor growth and metastasis of many cancers. However, the clinical significance and function of NEAT1 in osteosarcoma (OS) remain to be discovered. We here collected OS tissues (<i>n</i>=40) and adjacent non-tumor tissues (<i>n</i>=20) to determine the expression of NEAT1 and its clinical significance. NEAT1 was overexpressed in OS tissues, which positively correlated with tumor size, Enneking stage, and distant metastasis of OS patients. The elevated level of NEAT1 was confirmed in OS cell lines including MG63 and HOS <i>in vitro</i> Knockdown of NEAT1 by two siRNAs induced impaired cell vitalities, promoted the apoptosis, and G₀/G₁ arrest in two cell lines, which was associated with inhibited anti-apoptosis signals BCL-2 pathway and cell cycle-related cyclin D1 (CCND1) signals. Moreover, the tumor suppressor <i>miR-34c</i> was negatively regulated and inhibited by NEAT1 in OS. Suppression of <i>miR-34c</i> could up-regulate the expressions of its target genes <i>BCL-2</i> and <i>CCND1</i> to antagonize the effects of NEAT1 knockdown. Furthermore, overexpressed NEAT1 reduced the sensitivity of cisplatin (DDP) and inhibited DDP-induced apoptosis and cell cycle arrest via <i>miR-34c</i> The results <i>in vivo</i> also confirmed that knockdown of NEAT1 sensitized the OS cells to DPP-induced tumor regression, delayed the tumor growth with reduced levels of Ki-67, BCL-2, and cyclin D1 signals, suggesting that NEAT1 is an oncogene and chemotherapy resistant factor in OS.