MALAT1

MALAT1

The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a bona fide Long noncoding RNA (lncRNA). LncRNA MALAT1 was discovered as a prognostic factor for lung cancer metastasis but also has been linked to several other human tumor entities.


Ren et al. aimed to investigate the association of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) with acute ischemic stroke (AIS), and its association with disease severity, inflammation, and recurrence-free survival (RFS) in AIS patients. One hundred and twenty AIS patients and 120 controls were recruited. Venous blood samples from AIS patients (within 24 h after symptoms onset) and controls (at the entry to study) were collected to detect plasma lnc-MALAT1 expression by a real-time quantitative polymerase chain reaction. AIS severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Plasma concentrations of inflammation factors (including C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8, IL-10, IL-17, and IL-22) were measured and RFS was calculated. lnc-MALAT1 expression was decreased in AIS patients compared to controls, and it had a close correlation with AIS (AUC=0.791, 95% CI: 0.735-0.846). For disease condition, lnc-MALAT1 expression negatively correlated with NIHSS score and pro-inflammatory factor expression (including CRP, TNF-α, IL-6, IL-8, and IL-22), while it positively correlated with anti-inflammatory factor IL-10 expression. Furthermore, lnc-MALAT1 expression was elevated in AIS patients with diabetes. For prognosis, no statistical correlation of lnc-MALAT1 expression with RFS was found, while a trend for longer RFS was observed in patients with lnc-MALAT1 high expression compared to those with lnc-MALAT1 low expression 1).


lncRNAZFAS1 and MALAT1 were significantly upregulated (p < 0.05), whereas lncRNAs LINC00261 and LINC01619 were significantly downregulated in SAH patients with CVS (p < 0.05) compared to SAH patients without cerebral vasospasm (CV). Pan et al. applied this lncRNA signature to retrospectively predict CVS in SAH patients (n = 38 for SAH patients without CVS, and n = 27 for SAH patients with CVS). The 4-lncRNA signature was found to be predictive in >40% of samples and the 2-lncRNA comprising MALAT1 and LINC01619 accurately predicted CVS in ∼90% cases. These results are initial steps toward personalized management of SAH patients in clinics and provide novel CSF biomarkers that can substantially improve the clinical management of SAH patients 2).


lncRNA MALAT1 plays an important role on glioma progression and prognosis and may serve as a convictive prognostic biomarker for glioma patients 3) 4).


In a study, Fu et al. found that Malat1 expression and autophagy activity were significantly increased in glioma tissues compared with adjacent normal tissues. Additionally, Malat1 level was positively correlated with the expression of LC3-II (autophagy marker) mRNA in vivo. In vitro assays revealed that Malat1 significantly promoted autophagy activation and cell proliferation in glioma cells. More importantly, inhibition of autophagy by 3-MA relieved Malat1-induced cell proliferation. These data demonstrated that Malat1 activates autophagy and increases cell proliferation in glioma. We further investigated the molecular mechanisms whereby Malat1 functioned on glioma cell autophagy and proliferation. We found that Malat1 served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malat1 abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D. Overall, our study elucidated a novel Malat1-miR-101-STMN1/RAB5A/ATG4D regulatory network that Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma cells 5).


1)

Ren H, Wu F, Liu B, Song Z, Qu D. Association of circulating long non-coding RNA MALAT1 in diagnosis, disease surveillance, and prognosis of acute ischemic stroke. Braz J Med Biol Res. 2020 Oct 21;53(12):e9174. doi: 10.1590/1414-431×20209174. PMID: 33111743.
2)

Pan CY, Tian M, Zhang LL, et al. lncRNA Signature for Predicting Cerebral Vasospasm in Patients with SAH: Implications for Precision Neurosurgery [published online ahead of print, 2020 Jul 25]. Mol Ther Nucleic Acids. 2020;21:983-990. doi:10.1016/j.omtn.2020.07.028
3)

Ma KX, Wang HJ, Li XR, Li T, Su G, Yang P, Wu JW. Long noncoding RNA MALAT1 associates with the malignant status and poor prognosis in glioma. Tumour Biol. 2015 Jan 23. [Epub ahead of print] PubMed PMID: 25613066.
4)

Chen W, Xu XK, Li JL, Kong KK, Li H, Chen C, He J, Wang F, Li P, Ge XS, Li FC. MALAT1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing miR-203 and promoting thymidylate synthase expression. Oncotarget. 2017 Apr 4;8(14):22783-22799. doi: 10.18632/oncotarget.15199. PubMed PMID: 28187000; PubMed Central PMCID: PMC5410262.
5)

Fu Z, Luo W, Wang J, Peng T, Sun G, Shi J, Li Z, Zhang B. Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma. Biochem Biophys Res Commun. 2017 Aug 20. pii: S0006-291X(17)31629-7. doi: 10.1016/j.bbrc.2017.08.070. [Epub ahead of print] PubMed PMID: 28834690.

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