YY1-Regulated LINC00152 Promotes Triple Negative Breast Cancer Progression By Affecting On Stability Of PTEN Protein

Purposes We aim at studying the molecular mechanism of LINC00152 in the progression of triple negative breast cancer,so as to provide new ideas and potential targets for clinical treatment of triple negative breast cancer.Methods 52 breast cancer tissues and adjacent normal tissues were collected at the Thyroid and Breast Disease Institute,Union Hospital(Wuhan,China)during February 2015 to December 2016 and we compared the expression of LINC00152 in breast cancer and adjacent tissues and in 6 breast cell lines by fluorescence quantitative PCR.Correlation analysis of clinicopathological characteristics was performed in 572 breast cancer patients with TCGA database.The expression level of LINC00152 in MDA-MB-231 was decreased by using small interfering RNA while increased by using overexpressed plasmid vector.CHX assay and MG132 assay were used to verify the correlation between LINC00152 and protein PTEN stability by q RT-PCR and western blot,and Co-IP assay was used to explore both the ubiquitination level of PTEN and the ability of PTEN biding with ubiquitination ligase NEDD4 which was influenced by LINC00152.CHIP assay and luciferase reporter assay were used to verify the binding capacity and regulation between YY1 and LINC00152 promoter.Results LINC00152 expression in 52 breast cancer tissues was significantly higher than that in adjacent tissues.The expression of LINC00152 detected in 5 breast cancer cell lines,suggested that especially in triple negative breast cancer cells were highest than other cell lines.Statistical analysis showed that high expression of LINC00152 was an independent prognostic indicator of breast cancer.In knockout or overexpression experiments,LINC00152 did not regulate and inhibit the expression of PTEN at the transcriptional level,but affected the stability of PTEN by influencing the posttranslation modification.Co-IP experiment showed that the binding ability of PTEN to NEDD4 was positively regulated by LINC00152,and overexpression of LINC00152 increased the ubiquitination level of PTEN.The binding of YY1 and LINC00152 promoter negatively regulates the transcription of LINC00152 and inhibits the invasion and proliferation of LINC00152 in triple-negative breast cancer.Conclusions LINC00152 is negatively regulated by the transcription factor YY1 in triple-negative breast cancer,and plays a role in promoting cancer by regulating the stability of PTEN protein...