LINC00472 inhibits cell migration by enhancing intercellular adhesion and regulates H3K27ac level via interacting with P300 in Renal Clear Cell Carcinoma

Abstract

Renal clear cell carcinoma (RCCC) is the most common type of renal cell carcinoma, which is also difficult to diagnose and easy to metastasize. Currently, there is still a lack of effective clinical diagnostic indicators and treatment targets. This study aims to find effective diagnostic markers and therapeutic targets from the perspective of noncoding RNA. In this study, we found that the expression of Long noncoding RNA LINC00472 was significantly decreased in RCCC and showed a downward trend with the progression of cancer stage. Patients with low LINC00472 expression have poor prognosis. Inhibition of LINC00472 significantly increased cell proliferation and migration, while overexpression of LINC00472 obviously inhibited cell proliferation and enhanced intercellular adhesion. Transcriptome sequencing analysis demonstrated that LINC00472 was highly correlated with extracellular matrix and cell metastasis related pathways, and the consistent results were obtained by The Cancer Genome Atlas (TCGA) data analysis. Additionally, we discovered that the integrin family protein ITGB8 is a target gene of LINC00472. Mechanistically, we identified that LINC00472 interacts with histone acetyltransferase P300 to regulate the acetylation level of H3K27 at the ITGB8 transcription start site, which is the first time to elucidate its function in the regulation of histone modification. Our analysis results illustrated that LINC00472 can be used as a potential diagnosis marker of RCCC, and our mechanism researches provide a theoretical basis for the clinical development of new and effective treatment strategies.