The expression of the long NEAT1_2 isoform is associated with human epidermal growth factor receptor 2-positive breast cancers
Erik Knutsen, Seyed Mohammad Lellahi, Miriam R. R. Aure, Silje Nord, Silje Fismen, Kenneth Bowitz Larsen, Marta Tellez Gabriel, Annica Hedberg, Sunniva Bjørklund, Jürgen Geisler, Solveig Hofvind, Tone F. Bathen, Elin Borgen, Anne‐Lise Børresen‐Dale, Olav Engebråten, Øystein Garred, Gry Aarum Geitvik, Anita Langerød, Bjørn Naume, Hege G. Russnes, Ellen Schlichting, Ole Christian Lingjærde, Vessela N. Kristensen, Helle Kristine Skjerven, Thomas Papathomas, Olaf-Johan Hartman-Johnsen, Kristine Kleivi Sahlberg, Anna M. Bofin, Gunhild M. Mælandsmo, Thérese Sørlie, Elin Mortensen, Maria Perander
Abstract
The long non-coding RNA NEAT1 locus is transcribed into two overlapping isoforms, NEAT1_1 and NEAT1_2, of which the latter is essential for the assembly of nuclear paraspeckles. NEAT1 is abnormally expressed in a wide variety of human cancers. Emerging evidence suggests that the two isoforms have distinct functions in gene expression regulation, and recently it was shown that NEAT1_2, but not NEAT1_1, expression predicts poor clinical outcome in cancer. Here, we report that NEAT1_2 expression correlates with HER2-positive breast cancers and high-grade disease. We provide evidence that NEAT1_1 and NEAT1_2 have distinct expression pattern among different intrinsic breast cancer subtypes. Finally, we show that NEAT1_2 expression and paraspeckle formation increase upon lactation in humans, confirming what has previously been demonstrated in mice.