Lin28A promotes IRF6-regulated aerobic glycolysis in glioma cells by stabilizing SNHG14

Abstract

Warburg effect is a hallmark of cancer cells, wherein glycolysis is preferred over oxidative phosphorylation even in aerobic conditions. Reprogramming of glycometabolism is especially crucial for malignancy in glioma. RNA-binding proteins and long noncoding RNAs are important for aerobic glycolysis during malignant transformation. Thus, we determined the expression and function of RNA-binding protein Lin28A, long noncoding RNA SNHG14, and transcription factor IRF6 in human glioma cells to elucidate the mechanism(s) underlying their role in glycolysis. Quantitative real-time polymerase chain reaction and western blotting showed that Lin28A and SNHG14 were overexpressed and IRF6 was downregulated in glioma. Depleting Lin28A from cells decreased the stability and expression of SNHG14. Furthermore, depleting SNHG14 reduced IRF6 mRNA degradation by targeting its 3′ untranslated region and inhibiting STAU1-mediated degradation, thereby increasing the expression of IRF6. PKM2 is an important enzyme in aerobic glycolysis, and GLUT1 is the primary transporter that facilitates glucose uptake. IRF6 inhibited the transcription of PKM2 and GLUT1, thereby impairing glycolysis and cell proliferation and inducing apoptosis in glioma. Notably, depleting Lin28A and SNHG14 and overexpressing IRF6 reduced the growth of xenograft tumors in vivo and prolonged the survival of nude mice. Taken together, our data revealed that the Lin28A/SNHG14/IRF6 axis is crucial for reprogramming glucose metabolism and stimulating tumorigenesis in glioma cells. Thus, targeting this axis might help in the development of a novel therapeutic strategy for glioma metabolism.

WITHDRAWN: A Novel Long Non-coding RNA, ENSG00000236199, Inhibits Proliferation and Metastasis through NRIP1 by Sponging miR-576-5p in Hepatocellular Carcinoma

“…Although great progress has been made in the diagnosis and treatment for HCC, these achievements were far from improving the survival time and cure rate of HCC patients. More and more studies had shown that lncRNAs play an important role in various biological processes of human body (Wang et al 2020;Qu et al 2020;Lu et al 2020). In order to understand the development, diagnosis and treatment of the disease we need to explore the regulation mode of human gene deeply and immediately.…”

Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target

“…[3][4][5] Abnormal energy metabolism has also been reported in GBM and includes enhanced aerobic glycolysis and lipid synthesis to provide energy and raw materials to the highly proliferating cells. [6][7][8][9] Thus, key glycolipid metabolic enzymes and transcription factors are considered promising treatment targets and diagnostic and prognostic tumor markers for predictive, preventive, and personalized medicine. 10 Therefore, we proposed that targeting the cellular energy metabolism may be a new strategy for treating GBM.…”

“…12 RBP-Lin28A enhances the proliferation of GBM cells by improving the aerobic glycolytic capacity. 9 A recent study showed that Musashi RNA-binding protein 2 (MSI2) is highly expressed in GBM and stimulates the ability of GBM cells in proliferation, migration, and invasion. It also participates in regulating the resistance of GBM cells to temozolomide chemotherapy.…”

“…Chromatin immunoprecipitation (ChIP) assay was operated as previously described. 9 Immunoprecipitated DNA was amplified with the specific primer by PCR (shown in Table S4). For more details, please see Supporting Information of Materials and Methods.…”

Positive feedback between retinoic acid and 2-phospho-L-ascorbic acid trisodium salt during somatic cell reprogramming

“…2 a). Pscan software identified binding site of RARA::RARG on the promoters of Glut1 and Glut3 (Zambelli et al 2009 ; Meneses et al 2008 ; Lu et al 2020 ), which was confirmed when the activities of their promoters of (both wild type and RARA::RARG binding site mutation) were determined in the presence and absence of RA (Fig. 2 b-c).…”