Search Result

Basic Information

Classification Information

Regulatory Mechanism		Biological Function		Clinical Application
TF		Immune		Survival
Enhancer		Apoptosis		Drug
Variant		Cell Growth		Circulating
MiRNA		EMT		Metastasis
Methylation		Coding Ability		Recurrence

Cancer&Entry Information

Cancer Name	osteosarcoma
ICD-0-3	NA
Methods	Microarray, qPCR, Western blot, in vitro knockdown
Sample	The human osteosarcoma cell lines (U2OS, HOS, Saos2, 143B and MG63) and human osteoblast cell line (hFOB 1.19), cancerous osteosarcoma tissues and their adjacent nontumor tissues
Expression Pattern	down-regulated
Function Description	GAS5 was downregulated in cancerous osteosarcoma tissues and cells. Using a microarray analysis, we identified that GAS5 can regulate the expression of TP53, Bax, Bim, DDB2, TGFB and ROS1 in osteosarcoma cells. Specifically, GAS5 overexpression in the U2OS osteosarcoma cell line induced TP53, Bax and Bim levels but inhibited DDB2, TGFB and ROS1 expression, resulting in the inhibition of cell proliferation, invasion, colony formation and in vivo tumor formation. By analyzing the GAS5 promoter region (-2000), we identified several potential transcription factor-binding sites including NF-?B, IK-1, AP-1, SP1 and IRF1. only knockdown of IRF1 affected GAS5 expression.IRF1 formed a transcriptional complex with Histone Deacetylase 1 and 2 (HDAC1/2) and C-terminal binding protein 1 (CtBP1). Functional analyses indicated that the CtBP1-HDAC1/2-IRF1 complex specifically bound to the GAS5 promoter and regulated its expression and downstream events. Knockdown of CtBP1 or overexpression of IRF1 in osteosarcoma cells can significantly reverse their oncogenic phenotypes.
Pubmed ID	31337976
Year	2019
Title	The CtBP1-HDAC1/2-IRF1 transcriptional complex represses the expression of the long noncoding RNA GAS5 in human osteosarcoma cells

External Links