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.
Highlights
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
Cancer cells were identified by experienced pathologists, and NEAT1_2 expression was manually scored from “0” to “3” based on the presence and morphology of punctuated nuclear signals corresponding to paraspeckles (Fig. 1a)
We assessed the expression of NEAT1_2 by RNA-FISH and RT-qPCR in nine breast cancer cell lines classified according to the expression of hormone- and growth factor receptors into estrogen receptor (ER)/ progesterone receptor (PgR)-positive human epidermal growth factor receptor 2 (HER2)-negative cells (MCF7, T-47D), HER2-positive cells (BT474, HCC1569, SK-BR-3), and triple negative cells (BT549, Hs 578T, MDA-MB-231, MDA-MB-468)[43]
Summary
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. The long non-coding RNA (lncRNA) NEAT1 (Nuclear Paraspeckle Assembly Transcript 1) has recently gained considerable attention as it is abnormally expressed in human diseases, including cancer and neurodegenerative disorders. Cancer cells are exposed to a variety of extrinsic and intrinsic stressors like hypoxia, proteotoxicity, DNA damage, and reactive metabolic intermediates[24] Such malignancy-associated stress has been shown to induce NEAT1 expression and paraspeckle formation in vivo[15,16]. Focal deletions within the NEAT1 gene were found in 8% of breast cancers, and mutations are frequently found in the exonic region[38,39] This suggests that NEAT1 expression might either protect or enhance cancer initiation and progression dependent on tumor stage.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
