Long non‐coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL

Abstract

Glioma is the most common primary intracranial carcinoma with extremely poor prognosis. The significances of long non‐coding RNA (lncRNA) involved in glioma have been started revealed. However, the expression, roles and molecular mechanisms of most lncRNAs in glioma are still unknown. In this study, we identified a novel lncRNA LINC00526, which is significantly low expressed in glioma. Low expression of LINC00526 is correlated with aggravation and poor survival in glioma. Functional assays revealed that ectopic expression of LINC00526 inhibits glioma cell proliferation, migration, and invasion. LINC00526 silencing promotes glioma cell proliferation, migration and invasion. Mechanistically, we found that LINC00526 directly interacts with EZH2, represses the binding of EZH2 to AXL promoter, attenuates the transcriptional activating roles of EZH2 on AXL , and therefore represses AXL expression. Via repressing AXL, LINC00526 further represses PI3K/Akt/NF‐κB signalling. Intriguingly, we identified that NFKB1 and NFKB2 directly binds LINC00526 promoter and represses LINC00526 transcription. We further found that via activating NF‐κB signalling, AXL represses LINC00526 transcription. Therefore, LINC00526/EZH2/AXL/PI3K/Akt/NF‐κB form a feedback loop in glioma. Analysis of the TCGA data revealed that the expression of LINC00526 is inversely correlated with that of AXL in glioma tissues. In addition, functional rescue assays revealed that the tumour suppressive roles of LINC00526 are dependent on the negative regulation of AXL. Collectively, our data identified LINC00526 as a tumour suppressor in glioma via forming a double negative feedback loop with AXL. Our data also suggested LINC00526 as a potential prognostic biomarker and therapeutic candidate for glioma.

Rosmarinic Acid Induces Proliferation Suppression of Hepatoma Cells Associated with NF-κB Signaling Pathway

“…These results are similar to the reported role of RA in colorectal cancer [33]. Numerous studies have shown that the PI3K/Akt/NF-κB pathway is closely related to HCC progression [34][35][36]. In line with these reports, our results showed that the PI3K/Akt/NF-κB signal pathway is involved in the anti-tumor effects of RA in HCC.…”

Exosome‐transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma

“…Abnormal expression of Gas6/AXL has been confirmed in more and more human malignancies, including pancreatic cancer, breast cancer, NSCLC, glioma, and so on. 4,18 AXL promotes tumor cell self-renewal, EMT, and drug resistance, and it has become a novel attractive molecular target for anti-neoplastic drug discovery. 5,6,19,20 Studies demonstrated that AXL promoted osteosarcoma progression through activating AKT expression and that it was downregulated by F I G U R E 6 The expression of linc00852, AXL mRNA and miR-7-5p in osteosarcoma tissues and the relationship among them.…”

A six-gene prognostic model predicts overall survival in bladder cancer patients

“…Our result is consistent with the results of previous studies. LINC00526 is a long intergenic non-protein-coding RNA, and one study has demonstrated that it suppresses glioma progression [37]. ARL14 (ADP Ribosylation Factor Like GTPase 14) is a protein-coding gene that participates in GTP binding and signal transduction [38].…”