In the extracellular matrix (ECM), the glycosaminoglycan (GAG) hyaluronan (HA) has different physiological roles favouring hydration, elasticity and cell survival. Three different isoforms of HA synthases (HAS1, 2, and 3) are responsible for the production of HA. In several pathologies the upregulation of HAS enzymes leads to an abnormal HA accumulation causing cell dedifferentiation, proliferation and migration thus favouring cancer progression, fibrosis and vascular wall thickening. An intriguing new player in HAS2 gene expression regulation and HA production is the long non-coding RNA (lncRNA) hyaluronan synthase 2 antisense 1 (HAS2-AS1). A significant part of mammalian genomes corresponds to genes that transcribe lncRNAs; they can regulate gene expression through several mechanisms, being involved not only in maintaining the normal homeostasis of cells and tissues, but also in the onset and progression of different diseases, as demonstrated by the increasing number of studies published through the last decades. HAS2-AS1 is no exception: it can be localized both in the nucleus and in the cytosol, regulating cancer cells as well as vascular smooth muscle cells behaviour.
Keywords: 4-MU, 4-methylubelliferone; 4-MUG, 4-methylumbelliferyl glucuronide; Atherosclerosis; Cancer; ECM, extracellular matrix; EMT, epithelial to mesenchymal transition; Epigenetics; Extracellular matrix; GAG, glycosaminoglycans; Glycosaminoglycans; HA, hyaluronan; HAS2; HAS2, hyaluronan synthase 2; HAS2-AS1; HAS2–AS1, hyaluronan synthase 2 natural antisense 1; HIFs, hypoxia-inducible factors; NF-κB, nuclear factor κ–light-chain enhancer of activated B cell; PG, proteoglycan; PTM, post-translational modification; Proteoglycans; RBP, RNA-binding protein; SIRT1, sirtuin 1; SMCs, smooth muscle cells; TNF-α, tumour necrosis factor alpha; UDP-GlcNAc, UDP-N-acetylglucosamine; UDP-GlcUA, UDP-glucuronic acid; ceRNA, competitive endogenous RNA; lncRNA, long non-coding RNA; miRNA, micro-RNA.
© 2021 The Authors.