A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy

Abstract

BackgroundDespite the overwhelming number of investigations on AKT, little is known about lncRNA on AKT regulation, especially in GBM cells.MethodsRNA-binding protein immunoprecipitation assay (RIP) and RNA pulldown were used to confirm the binding of LINC00470 and fused in sarcoma (FUS). Confocal imaging, co-immunoprecipitation (Co-IP) and GST pulldown assays were used to detect the interaction between FUS and AKT. EdU assay, CCK-8 assay, and intracranial xenograft assays were performed to demonstrate the effect of LINC00470 on the malignant phenotype of GBM cells. RT-qPCR and Western blotting were performed to test the effect of LINC00470 on AKT and pAKT.ResultsIn this study, we demonstrated that LINC00470 was a positive regulator for AKT activation in GBM. LINC00470 bound to FUS and AKT to form a ternary complex, anchoring FUS in the cytoplasm to increase AKT activity. Higher pAKT activated by LINC00470 inhibited ubiquitination of HK1, which affected glycolysis, and inhibited cell autophagy. Furthermore, higher LINC00470 expression was associated with GBM tumorigenesis and poor patient prognosis.ConclusionsOur findings revealed a noncanonical AKT activation signaling pathway, i.e., LINC00470 directly interacts with FUS, serving as an AKT activator to promote GBM progression. LINC00470 has an important referential significance to evaluate the prognosis of patients.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0619-z) contains supplementary material, which is available to authorized users.

LINC00470 promotes tumour proliferation and invasion, and attenuates chemosensitivity through the LINC00470/miR‐134/Myc/ABCC1 axis in glioma

“…9 In our previous studies, we found that LINC00470 activated the AKT signalling pathway and promoted the tumour growth of intracranial transplantation mouse model with glioma. 10 However, the role and mechanism of LINC00470 in glioma must be further elucidated; in particular, it remains unclear whether LINC00470 affects the chemosensitivity of glioma.…”

Identification of biomarkers and pathways in hypertensive nephropathy based on the ceRNA regulatory network

“…KCTD21-AS1, which promoted protein degradation and reduced cellular signaling, was associated with many diseases, including breast cancer [34] and obesity [35]. A study by Liu et al indicated that LINC00470 was up-regulated in glioblastoma cell and its high level expression was an unfavorable prognosis marker for astrocytoma patients [36]. Moreover, SNHG14, as a key lncRNA, facilitated the migration and invasion of clear cell renal cell carcinoma via sponging miR-203 and accelerate Neural Wiskott-Aldrich syndrome protein [37].…”

Long Non-Coding RNA LINC00663 Promotes Gliomagenesis and Progression

“…Multitudes of studies have demonstrated the importance of PI3K in the activation of AKT, while evidence suggests that AKT activation can proceed by the PI3K independent manner [27]. Several lncRNAs (LINK-A, lncRNA OIP5-AS1, MALAT1 and LINC00470) promote the over activation of AKT signaling [28][29][30][31]. In this study, Western blot analysis results con rmed AKT activity was apparently suppressed in U87 cells but slightly in U251 cells with LINC00663 knockdown, without affecting mTOR in the AKT pathway, which was worthy of attention in the future.…”