Long Intergenic Noncoding RNA 00511 Acts as an Oncogene in Non–small-cell Lung Cancer by Binding to EZH2 and Suppressing p57

Abstract

Long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis. However, the function and mechanism of lncRNAs in human non–small-cell lung cancer (NSCLC) are still remaining largely unknown. Long intergenic noncoding RNA 00511 (LINC00511) has been found to be upregulated and acts as an oncogene in breast cancer, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Herein, we identified LINC00511 as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found LINC00511 was upregulated and associated with oncogenesis, tumor size, metastasis, and poor prognosis in NSCLC. Moreover, LINC00511 affected cell proliferation, invasiveness, metastasis, and apoptosis in multiple NSCLC cell lines. Mechanistically, LINC00511 bound histone methyltransferase enhancer of zeste homolog 2 ((EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2), a highly conserved protein complex that regulates gene expression by methylating lysine 27 on histone H3), and acted as a modular scaffold of EZH2/PRC2 complexes, coordinated their localization, and specified the histone modification pattern on the target genes, including p57, and consequently altered NSCLC cell biology. Thus, LINC00511 is mechanistically, functionally, and clinically oncogenic in NSCLC. Targeting LINC00511 and its pathway may be meaningful for treating patients with NSCLC.

LncRNA SNHG6 is Associated with Poor Prognosis of Gastric Cancer and Promotes Cell Proliferation and EMT through Epigenetically Silencing p27 and Sponging miR-101-3p

“…And the aberrant methylation such as PRC2-mediated histone methylation in the CKI gene promoter region is associated with gene expression suppression [36-39]. Additionally, plenty of lncRNAs have been reported to modulate specific genetic loci through recruiting PRC2 and PRC2-mediated epigenetic regulation play important role in tumorigenesis [17, 30, 31, 40-42]. In present study, our finding demonstrated that the deletion of SNHG6 could epigenetically silence the expression of p27 through interacting with EZH2.…”

HNRNPAB‐regulated lncRNA‐ELF209 inhibits the malignancy of hepatocellular carcinoma

“…The highly complex nature of lncRNAs indicates that these are key regulators in cellular process and tumor progression. LncRNAs have been identified as potential biomarkers and therapeutic targets for human cancers . However, the mechanisms by which lncRNAs are transcriptionally regulated and their roles in HCC progression have not been fully elucidated.…”

Long noncoding RNAs in autoimmune diseases

“…This regulatory mechanism is very beneficial for the body/cell to generate feedback and regulation based on external signals and stimuli. lincRNA00511 acts as a modular scaffold of EZH2/PRC2 complexes, coordinating their localization, and regulates histone modification patterns of target genes, including p57, consequently altering tumor cellular biology …”