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

SIMPLE SUMMARY: Altered metabolism is a hallmark of most cancers. The way that cancer cells regulate their energy production to fuel constant proliferation has been of interest with the hope that it may be exploited therapeutically. The long noncoding RNA, NEAT1, is often dysregulated in tumours. NEAT1 RNA can be transcribed as two isoforms with different lengths, with each variant responsible for different functions. This review explores how the isoforms contribute to cancer metabolism. ABSTRACT: The long noncoding RNA NEAT1 is known to be heavily dysregulated in many cancers. A single exon gene produces two isoforms, NEAT1_1 and NEAT1_2, through alternative 3′-end processing. As the longer isoform, NEAT1_2 is an essential scaffold for nuclear paraspeckle formation. It was previously thought that the short NEAT1_1 isoform only exists to keep the NEAT1 locus active for rapid paraspeckle formation. However, a recent glycolysis-enhancing function for NEAT1_1, contributing to cancer cell proliferation and the Warburg effect, has been demonstrated. Previous studies have mainly focused on quantifying total NEAT1 and NEAT1_2 expression levels. However, in light of the NEAT1_1 role in cancer cell metabolism, the contribution from specific NEAT1 isoforms is no longer clear. Here, the roles of NEAT1_1 and NEAT1_2 in metabolism and cancer progression are discussed.