Long noncoding RNA OVAAL enhances nucleotide synthesis through pyruvate carboxylase to promote 5-fluorouracil resistance in gastric cancer.

ABSTRACT: 5-Fluorouracil (5-FU) is widely used in gastric cancer treatment, yet 5-FU resistance remains an important clinical challenge. We established a model based on five long noncoding RNAs (lncRNA) to effectively assess the prognosis of gastric cancer patients; among them, lncRNA OVAAL was markedly upregulated in gastric cancer and associated with poor prognosis and 5-FU resistance. In vitro and in vivo assays confirmed that OVAAL promoted proliferation and 5-FU resistance of gastric cancer cells. Mechanistically, OVAAL bound with pyruvate carboxylase (PC) and stabilized PC from HSC70/CHIP-mediated ubiquitination and degradation. OVAAL knockdown reduced intracellular levels of oxaloacetate and aspartate, and the subsequent pyrimidine synthesis, which could be rescued by PC overexpression. Moreo

SUBMITTER: Tan JN 

PROVIDER: S-EPMC9459305 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature