Long Non-Coding RNAs and Metabolic Rewiring in Pancreatic Cancer

SIMPLE SUMMARY: Altered metabolism is one of the main driving forces of pancreatic cancer development, progression, and response to treatment. Long non-coding RNAs, which regulate multiple cellular functions, are frequently aberrantly expressed in pancreatic cancer. As lncRNAs can be measured in tissue and plasma, and can be silenced by different mechanisms, there is growing interest in their potential as biomarkers and/or therapeutic targets. Considering that several lncRNAs are implicated in metabolic homeostasis, this review focuses on the impact of lncRNA disruption in pancreatic cancer metabolic rewiring. ABSTRACT: Pancreatic adenocarcinoma is a highly aggressive disease with a poor prognosis. The reprogramming of energetic metabolism has long been implicated in pancreatic tumorigenesis and/or resistance to treatment. Considering that long non-coding RNA dysregulation has been described both in cancerogenesis and in the altered homeostasis of several metabolic pathways, metabolism-associated lncRNAs can contribute to pancreatic cancer evolution. The objective of this review is to assess the burden of lncRNA dysregulation in pancreatic cancer metabolic reprogramming, and its effect on this tumor’s natural course and response to treatment. Therefore, we reviewed the available literature to assess whether metabolism-associated lncRNAs have been found to be differentially expressed in pancreatic cancer, as well as whether experimental evidence of their role in such pathways can be demonstrated. Specifically, we provide a comprehensive overview of lncRNAs that are implicated in hypoxia-related pathways, as well as in the reprogramming of autophagy, lipid metabolism, and amino acid metabolism. Our review gathers background material for further research on possible applications of metabolism-associated lncRNAs as diagnostic/prognostic biomarkers and/or as potential therapeutic targets in pancreatic adenocarcinoma.