Ontology highlight
ABSTRACT: Background
Gastric cancer (GC) is one of the most common types of cancer worldwide, which leads to more than 10% of cancer-related deaths. Metabolism reprogramming presents as a pivotal event in cancer initiation and progression through enhancing aerobic glycolysis and anabolic metabolism. However, the underlying regulatory mechanisms in GC remain unknown.Methods
VAL was identified by bioinformatics analyses in GC. Cell-based assays and mouse model illustrate the role of VAL in GC. RNA pull-down, immunoprecipitation assay and Western blot elucidate the interaction between VAL and PKM2. Pyruvate kinase activity, ECAR and OCR were measured to validate aerobic glycolysis of GC cells.Results
Long non-coding RNA (lncRNA) VAL is significantly upregulated in GCs and indicates poor prognosis. Functional assays showed that VAL promotes GC malignant progression. Mechanistically, VAL strengthens the enzymatic activity of PKM2 and aerobic glycolysis of GC cells through directly binding with PKM2 to abrogate the PKM2-Parkin interaction, and to suppress Parkin-induced polyubiquitination of PKM2. In addition, glucose starvation induces VAL expression to enhance this process.Conclusions
Our study provides an insight into an lncRNA-dependent regulation on the enzymatic activity of PKM2, and suggests a potential of targeting VAL or PKM2 as promising biomarkers in GC diagnosis and treatment.
SUBMITTER: Dai T
PROVIDER: S-EPMC9561166 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Dai Ting T Zhang Xin X Zhou Xiang X Hu Xiaoxia X Huang Xiaodi X Xing Feiyue F Tian Han H Li Yun Y
Clinical and translational medicine 20221001 10
<h4>Background</h4>Gastric cancer (GC) is one of the most common types of cancer worldwide, which leads to more than 10% of cancer-related deaths. Metabolism reprogramming presents as a pivotal event in cancer initiation and progression through enhancing aerobic glycolysis and anabolic metabolism. However, the underlying regulatory mechanisms in GC remain unknown.<h4>Methods</h4>VAL was identified by bioinformatics analyses in GC. Cell-based assays and mouse model illustrate the role of VAL in G ...[more]