LncRNA NEAT1 facilitates glioma progression via stabilizing PGK1

Abstract

Background Long noncoding RNA NEAT1 has been implicated in glioma progression. However, the effect of NEAT1 on glycolysis of glioma cell and the potential mechanism remain unclear. Methods In vitro experiments, including CCK-8, colony formation, ECAR, and lactate detection assays were performed to evaluate the effect of NEAT1 on proliferation and glycolysis of glioma cell. RNA pulldown and RIP assays were performed to identify the interaction between NEAT1 and PGK1. Truncated mutation of NEAT1 and PGK1 was used to confirm the specific interactive domains between NEAT1 and PGK1. Animal studies were performed to analyze the effect of NEAT1/PGK1 on glioma progression. Results NEAT1 knockdown significantly suppressed the proliferation and glycolysis of glioma cells. NEAT1 could specifically interact with PGK1, which promotes PGK1 stability. Hairpin A of NEAT1 is essential for interaction with M1 domain of PGK1. Depletion of NEAT1 markedly inhibited tumor growth in mice, while PGK1 could reverse this effect. Higher expression of NEAT1 was associated with poor overall survival of GBM patients. Conclusions NEAT1 over expression promotes glioma progression through stabilizing PGK1. NEAT1/PGK1 axis is a candidate therapeutic target for glioma treatment.

Molecular Interactions of the Long Noncoding RNA NEAT1 in Cancer

“…Since NEAT1 belongs to the family of nucleotides, it has the ability to interact with other nucleotides, including mRNA, miRNA, or DNA, to change the expression of downstream proteins. In addition, the secondary structure of NEAT1 can capture some proteins and change their stability or molecular function [ 6 ].…”

M7G-related LncRNAs: A comprehensive analysis of the prognosis and immunity in glioma

“…In addition, there are pieces of evidence that lncRNAs play an essential part in cancer ( Ho et al, 2022 ; Liang et al, 2022 ; Zhang et al, 2022 ). SNAI3-AS1 , an m 7 G prognosis-associated lncRNA, is an important tumor modifier in hepatocellular carcinoma tumor progression ( Li et al, 2020 ).…”

The Long and the Short of It: NEAT1 and Cancer Cell Metabolism

“…Interestingly, the depletion of pinin reduces cytoplasmic NEAT1_1 even after glucose stimulation, indicating the importance of pinin in the nucleocytoplasmic transport of NEAT1_1 [ 12 ]. Importantly, in the cytoplasm, NEAT1_1 interacts with the glycolytic enzymes phosphoglycerate kinase (PGK1), phosphoglycerate mutase (PGAM1), and alpha enolase (ENO1) to promote glycolysis, enhancing growth, proliferation, invasion, and metastasis ( Figure 2 ) [ 12 , 15 ].…”

“…Hydrophilic proteins bind 3′ and 5′ regions of the NEAT1_2 transcript to form the paraspeckle shell, whilst the middle segment of the transcript forms the hydrophobic core [ 8 , 10 , 38 , 42 ]. Individual paraspeckles are spheroidal, but during stress conditions, they can be linked together to generate elongated paraspeckle structures [ 15 ]. In HeLa cells, there are ~5–20 paraspeckles per nucleus [ 43 ].…”