Research Paper|Volume 11, Issue 18|pp 7678—7693

Long noncoding RNA TTN-AS1 enhances the malignant characteristics of osteosarcoma by acting as a competing endogenous RNA on microRNA-376a thereby upregulating dickkopf-1

Shenglong Li¹, Fei Liu¹, Yi Pei¹, Wei Wang¹, Ke Zheng¹, Xiaojing Zhang¹

¹Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning, P.R. China

Received: August 2, 2019Accepted: September 5, 2019Published: September 16, 2019

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The expression levels and detailed functions of TTN-AS1 in osteosarcoma (OS) have not yet been explored. This study aimed to measure TTN-AS1 expression in OS tissues and cell lines, investigate its specific roles in the aggressive characteristics of OS cells in vitro and in vivo, and elucidate the regulatory mechanisms of TTN-AS1 action. TTN-AS1 expression was high in OS tissue samples and cell lines; TTN-AS1 overexpression correlated with the clinical stage, distant metastasis, and shorter overall survival of the patients. A TTN-AS1 knockdown inhibited OS cell proliferation, migration, and invasion and induced apoptosis in vitro and slowed tumor growth in vivo. Mechanism investigation revealed that TTN-AS1 acts as a competing endogenous RNA on microRNA-376a-3p (miR-376a) in OS cells. Dickkopf-1 (DKK1) mRNA was identified as a direct target of miR-376a in OS cells. Resumption of DKK1 expression reversed the tumor-suppressive activities of miR-376a overexpression in OS cells. The knockdown of miR-376a counteracted the reduction in the malignant characteristics of OS cells by the downregulation of TTN-AS1. In conclusion, TTN-AS1 functions as a competing endogenous RNA targeting miR-376a and increases the malignancy of OS cells in vitro and in vivo by upregulating DKK1.