A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy
Authors: Yingnan Sun
Yan Zhang
Xiaoling She
Minghua Wu
Peiyao Li
Qiang Liu
Jianbo Feng
Chunhua Zhao
Haijuan Fu
Qing Liu
Li Fan
Changhong Liu
Journal: Journal of Hematology & Oncology (2018)
Discipline: CLINICAL MEDICINE
Keywords: AKT activation; GBM; LncRNA; Oncogene.
Affiliations: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, 410006, Hunan, China., Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, 410078, Hunan, China., Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410078, Hunan, China., Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, 410078, Hunan, China., Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China., Department of Biochemistry, University of California, Riverside, CA, 92521, USA., Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China., Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China., Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, 410078, Hunan, China. ., Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410078, Hunan, China. ., Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, 410078, Hunan, China. .

Abstract:  Background: Despite the overwhelming number of investigations on AKT, little is known about lncRNA on AKT regulation, especially in GBM cells. Methods: RNA-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. Results: In 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. Conclusions: Our 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. 

Retracted: No

PubPeer comments:
 The authors in this paper proposed a notion called u201cFermatean fuzzy linguistic term setsu201d (Definition 6). In Definition 12, the authors defined some u201cdistance measuresu201d and claimed in **Theorem 5** that $$D_{FG}(l_1, l_2) =0 quad text{if and only if}quad l_1 =l_2$$ However, **such a claim is obviously not correct** although a proof was provided. For example, let $$l_1 = (s_0, 1, 0)$$ $$l_2 = (s_0, 0, 1)$$ According to the definition of $D_{FG}$ in eq.(3.7), $$D_{FG}(l_1, l_2) =0$$ but it is clear that $$l_1 eq l_2$$ In other words, **Theorem 5 and its proof are invalid.** ![file] ![file] ![file] ,