Long noncoding RNAMALAT1-derived mascRNA is involved in cardiovascular innate immunity

Abstract

Long noncoding RNA MALAT1-derived mascRNA is involved in cardiovascular innate immunity Dear Editor, Next-generation sequencing revealed that the majority of the human genome is transcribed but has no coding function. It is estimated that .30000 long noncoding RNAs (lncRNAs) are expressed in humans, but their functions are largely unknown (Suckau et al., 2009; Rinn and Chang, 2012; Poller et al., 2013). Consideration of noncoding genomic elements in pathogenetic studies is warranted and enabled by technological advances allowing comprehensive transcriptome mapping of protein-coding genes as well as small and long ncRNAs. We searched for lncRNAs influencing antiviral capacity in patients with Coxsackievirus B3 (CVB3) cardiomyopathy (Kuhl et al., 2012) and assign here immunoregulatory functions to the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and its enzymatic processing product MALAT1associated small cytoplasmic RNA (mascRNA). Some lncRNAs undergo complex posttranscriptional processing (Wilusz et al., 2008; Kuhn et al., 2015). The MALAT1-mascRNA system is particularly interesting in this regard, since the 7-kb primary transcript localizes to the nucleus (Tripathi et al., 2010), whereas the small MALAT1-derived mascRNA is found exclusively in the cytoplasm. MALAT1 has not previously been studied in the context of infectious or immunological diseases, but it is highly expressed in tumors and associated with metastasis (Nakagawa et al., 2012). Recent studies additionally report that MALAT1 regulates endothelial cell functions and angiogenesis in vitro and in vivo (Michalik et al., 2014). For the first time, our new data now indicate that the MALAT1-mascRNA system has important immunoregulatory functions as well. Moreover, we document regulatory and functional dichotomy in the MALAT1

The role of lncRNA MALAT1 in cardiovascular disease

“…However, MALAT1 was also found to induce antiviral immunity in patients with coxsackievirus B3 (CVB3) cardiomyopathy or CVB‐infected rats . MALAT1 increased expressions of NOS2 and tripartite motif 10, both of which are involved in antiviral immunity, and T cell markers CD4 and CD8 …”

“…In addition, MALAT1 was also found to enhance palmitic acid induced apoptosis of cardiomyocytes by sponging miR‐26a to activate TLR4/NF‐κB‐mediated inflammatory response and up‐regulate the expression of HMGB1 . However, MALAT1 was also found to induce antiviral immunity in patients with coxsackievirus B3 (CVB3) cardiomyopathy or CVB‐infected rats . MALAT1 increased expressions of NOS2 and tripartite motif 10, both of which are involved in antiviral immunity, and T cell markers CD4 and CD8 …”

“…75 MALAT1 increased expressions of NOS2 and tripartite motif 10, both of which are involved in antiviral immunity, and T cell markers CD4 and CD8. 75…”

Long Non-Coding RNAs Link Oxidized Low-Density Lipoprotein With the Inflammatory Response of Macrophages in Atherogenesis

“…Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was first found in non-small cell lung cancer and also found to be upregulated in high-fat diet ApoE −/− mice and patients with unstable angina (109,110). MALAT1 could protect HUVECs against ox-LDLinduced apoptosis by upregulating endothelial-to-mesenchymal transition (EndMT), which is associated with plaque instability in vitro (77).…”

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

“…For examples, lncRNA MALAT1 could induced migration and invasion of human breast cancer cells by competitively binding miR-1 with cdc42 [28]. MALAT1-derived mascRNA is involved in cardiovascular innate immunity [29]. And downregulation of MALAT1 affects proliferation and the expression of stemness markers in glioma stem cell line SHG139S [30].…”