Long Noncoding RNA SNHG7 Promotes the Tumor Growth and Epithelial-to-Mesenchymal Transition via Regulation of miR-34a Signals in Osteosarcoma

Abstract

The long noncoding RNA (LncRNA) SNHG7 (small nuclear RNA host gene 7) is a novel LncRNA and functions as an oncogene to promote tumor proliferation and inhibits apoptosis in many cancers. However, the role of SNHG7 in osteosarcoma (OS) remains to be further investigated. In this study, OS tissues and corresponding relative normal tissues (n = 30) were collected to determine the expression of SNHG7 in OS. The results indicated that high SNHG7 level in OS correlated with high Enneking stage, distant metastasis, and short overall survival time of OS patients. Moreover, miRNA-34a (miR-34a) is a classic tumor suppressor. Bioinformatic analysis predicted that SNHG7 harbored miR-34a binding sites, and the authors found that SNHG7 negatively correlated with miR-34a in OS tissues and the SNHG7 inhibition induced the restoration of miR-34a in OS cell lines MG63 and SaOS2, leading to the reactivation of miR-34a-mediated tumor suppression. Knockdown of SNHG7 in tumor cells significantly impaired the cell vitality, migration and invasion or TGF-β-induced epithelial-mesenchymal transition (EMT), induced apoptosis, and G1/S arrest via miR-34a. Mechanistically, the targets of miR-34a could be upregulated by SNHG7, including proliferation-related Notch1, apoptosis-related BCL-2, cell cycle-related CDK6, and EMT-related SMAD4. The oncogene role of SNHG7 in vivo was also confirmed and found that knockdown of SNHG7 delayed the tumor growth with increased miR-34a level and Ki-67 level in OS tissues. These findings demonstrated that the LncRNA SNHG7 is upregulated during the development of OS via inhibition of tumor suppressor miR-34s signals.

Keywords: EMT; SNHG7; lncRNA; miR-34a; osteosarcoma; prognosis.