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LncRNA‐XIST/microRNA‐126 sponge mediates cell proliferation and glucose metabolism through the IRS1/PI3K/Akt pathway in glioma
Author(s) -
Cheng Zhihua,
Luo Cong,
Guo Zhilin
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29440
Subject(s) - xist , biology , pi3k/akt/mtor pathway , gene knockdown , protein kinase b , cancer research , glioma , long non coding rna , irs1 , microrna , competing endogenous rna , viability assay , glucose transporter , glucose uptake , cell growth , microbiology and biotechnology , cell , signal transduction , rna , insulin receptor , apoptosis , endocrinology , insulin , biochemistry , insulin resistance , x chromosome , gene , x inactivation
Abnormal glucose metabolism may contribute to cancer progression. Glioma represents a cancer resulting from an imbalance between glucose metabolism and tumor growth. However, the molecular mechanisms responsible for dysregulated brain glucose metabolism and lactate accumulation in glioma remain to be elucidated. The present study identified a long noncoding RNA (lncRNA) X‐inactive specific transcript (XIST) as a candidate to mediate glucose metabolism in glioma. Cell viability, migration, invasion, and resistance to apoptosis were evaluated in lncRNA‐XIST‐depleted glioblastoma cells by short hairpin RNA. Glucose uptake, lactate production, as well as levels of glucose transporter 1 (GLUT1) and GLUT3, were measured. Luciferase assay, RNA pull‐down, and RNA immunoprecipitation were performed to validate the interactions among lncRNA‐XIST, microRNA‐126 (miR‐126), and insulin receptor substrate 1 (IRS1). An in vivo analysis was carried out in nude mice bearing glioblastoma cell xenografts. The study found that lncRNA‐XIST knockdown inhibited cell viability, migration, invasion, resistance to apoptosis, and glucose metabolism of glioblastoma cells. LncRNA‐XIST functioned as a competing endogenous RNA of miR‐126 and then regulated IRS1/PI3K/Akt pathway in glioblastoma cells. In vivo results demonstrated lncRNA‐XIST knockdown reduces the tumorigenicity of glioblastoma cells. Taken together, we demonstrated a novel cellular mechanism that was dependent of the lncRNA‐XIST/miR‐126/IRS1/PI3K/Akt pathway in enhanced glucose metabolism in glioma.