LINC00891 Attenuates the Proliferation and Metastasis of Osteosarcoma Cells via miR-27a-3p/TET1 Axis

Abstract

Objective: There is currently no adequate treatment for osteosarcoma, a bone malignancy that poses a serious threat to adolescents and children. The dysregulation of long noncoding RNAs is associated with many cancers, including osteosarcoma. LINC00891 expression is aberrant in endometrial cancer, lung cancer, and thyroid cancer, and likely regulate the malignant behavior of cancer. However, the potential function and mechanisms of LINC00891 in osteosarcoma progression remain unclear. Materials and Methods: LINC00891, miR-27a-3p, and TET1 mRNA expression in osteosarcoma cells were analyzed using quantitative reverse transcription-polymerase chain reaction. CCK-8 and Transwell experiments were performed on osteosarcoma cells to investigate proliferation, migration, and invasion, respectively. Ten-eleven translocation 1 (TET1) protein was analyzed using western blotting. Luciferase experiment was performed to investigate the interactions between LINC00891 with miR-27a-3p, and miR-27a-3p with TET1. Results: LINC00891 expression was dramatically decreased in the five osteosarcoma cell lines examined, particularly in 143B and SaoS-2 cells. LINC00891 overexpression due to plasmid transfection sharply blocked the proliferation, migration, and invasion of osteosarcoma cells. Dual-luciferase reporter experiments found that LINC00891 sponges miR-27a-3p, and LINC00891 overexpression sharply decreases miR-27a-3p expression. Transfection with miR-27a-3p mimic accelerated the malignant behaviors in LINC00891 overexpressed-osteosarcoma cells. Moreover, TET1 was a novel targeted-gene of miR-27a-3p. TET1 protein was significantly impeded, whereas LINC00891 overexpression elevated TET1 mRNA and protein in osteosarcoma cells. MiR-27a-3p overexpression inhibited TET1 mRNA and protein in osteosarcoma cells. Conclusions: Our study verified that LINC00891 attenuates the proliferation and metastasis of osteosarcoma cells via the miR-27a-3p/TET1 axis. This study clarifies a new mechanism and therapeutic target for the development of osteosarcoma.

Keywords: LINC00891; TET1; metastasis; miR-27a-3p; osteosarcoma; proliferation.