Long Non-Coding RNA TUG1 Promotes Proliferation and Inhibits Apoptosis of Osteosarcoma Cells by Sponging miR-132-3p and Upregulating SOX4 Expression.
10.3349/ymj.2018.59.2.226
- Author:
Gang LI
1
;
Keyu LIU
;
Xinhui DU
Author Information
1. Department of Orthopedics, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China. liganghavst@163.com
- Publication Type:Original Article
- Keywords:
Osteosarcoma;
TUG1;
miR-132-3p;
SOX4
- MeSH:
Apoptosis/*genetics;
Biomarkers, Tumor;
Bone Neoplasms/genetics/metabolism/*pathology;
Cell Line, Tumor;
Cell Proliferation;
Gene Expression Regulation, Neoplastic/genetics;
Gene Knockdown Techniques;
Humans;
MicroRNAs/*genetics/metabolism;
Osteosarcoma/genetics/metabolism/*pathology;
RNA, Long Noncoding/*genetics/metabolism;
Real-Time Polymerase Chain Reaction;
Reverse Transcriptase Polymerase Chain Reaction;
SOXC Transcription Factors/genetics/*metabolism;
Transcriptional Activation;
Tumor Cells, Cultured;
Up-Regulation
- From:Yonsei Medical Journal
2018;59(2):226-235
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Long non-coding RNA taurine upregulated gene 1 (TUG1) is reported to be a vital regulator of the progression of various cancers. This study aimed to explore the exact roles and molecular mechanisms of TUG1 in osteosarcoma (OS) development. MATERIALS AND METHODS: Real-time quantitative PCR was applied to detect the expressions of TUG1 and microRNA-132-3p (miR-132-3p) in OS tissues and cells. Western blot was performed to measure protein levels of sex determining region Y-box 4 (SOX4). Cell viability was assessed using XTT assay. Cell apoptosis was evaluated using flow cytometry and caspase-3 activity detection assays. Bioinformatics analysis and luciferase reporter experiments were employed to confirm relationships among TUG1, miR-132-3p, and SOX4. RESULTS: TUG1 was highly expressed in human OS tissues, OS cell lines, and primary OS cells. TUG1 knockdown hindered proliferation and induced apoptosis in human OS cell lines and primary OS cells. Moreover, TUG1 inhibited miR-132-3p expression by direct interaction, and introduction of miR-132-3p inhibitor partly abrogated the effect of TUG1 knockdown on the proliferation and apoptosis of OS cells. Furthermore, SOX4 was validated as a target of miR-132-3p. Further functional analyses revealed that miR-132-3p inhibited proliferation and induced apoptosis of OS cells, while this effect was greatly abated following SOX4 overexpression. Moreover, TUG1 knockdown suppressed proliferation and promoted apoptosis by upregulating miR-132-3p and downregulating SOX4 in primary OS cells. CONCLUSION: TUG1 facilitated proliferation and suppressed apoptosis by regulating the miR-132-3p/SOX4 axis in human OS cell lines and primary OS cells. This finding provides a potential target for OS therapy.
