Long Noncoding RNA MALAT1 Promotes Aggressive Pancreatic Cancer Proliferation and Metastasis via the Stimulation of Autophagy
Open Access
- 1 September 2016
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Therapeutics
- Vol. 15 (9), 2232-2243
- https://doi.org/10.1158/1535-7163.mct-16-0008
Abstract
Recently, pancreatic ductal adenocarcinoma (PDAC) has emerged as one of the most aggressive malignant tumors with the worst prognosis. Previous studies have demonstrated that long non-coding RNA MALAT1 is increased in pancreatic cancer and is identified as a diagnostic biomarker. Nonetheless, the molecular mechanism of elevated MALAT1 levels and tumor aggressiveness remains unknown. In this study, MALAT1 was found to be highly expressed in PDAC tissues, and elevated expression was associated with poorer prognoses. Additionally, MALAT1 was positively linearly correlated with the expression of LC3B mRNA. Furthermore, several molecules involved in cellular autophagic flux were modulated following the downregulation of MALAT1, including LC3, P62 and LAMP-2. Mechanistically, we found that MALAT1 interacted with RNA binding protein HuR, and silencing of MALAT1 greatly enhanced the posttranscriptional regulation of TIA-1 and had further effects on inhibiting autophagy. MALAT1 was speculated to regulate tumorigenesis via HuR-TIA-1 mediated autophagic activation. Hence, we investigated the biological properties of MALAT1 in terms of tumor proliferation and metastasis by promoting autophagy in vitro. In brief, these data demonstrate that MALAT1 could facilitate the advanced progression of tumors in vivo. Our study highlights the new roles of MALAT1 on pro-tumorigenic functioning and anti-cancer therapy via activating autophagy in pancreatic cancer.This publication has 46 references indexed in Scilit:
- T-cell Intracellular Antigen (TIA)-Proteins Deficiency in Murine Embryonic Fibroblasts Alters Cell Cycle Progression and Induces AutophagyPLOS ONE, 2013
- Pristimerin Causes G1 Arrest, Induces Apoptosis, and Enhances the Chemosensitivity to Gemcitabine in Pancreatic Cancer CellsPLOS ONE, 2012
- KrasG12D-Induced IKK2/β/NF-κB Activation by IL-1α and p62 Feedforward Loops Is Required for Development of Pancreatic Ductal AdenocarcinomaCancer Cell, 2012
- Nuclear Factor-κB–Dependent Epithelial to Mesenchymal Transition Induced by HIF-1α Activation in Pancreatic Cancer Cells under Hypoxic ConditionsPLOS ONE, 2011
- Autophagy facilitates glycolysis during Ras-mediated oncogenic transformationMolecular Biology of the Cell, 2011
- Pancreatic CancerThe New England Journal of Medicine, 2010
- Long noncoding RNAs: functional surprises from the RNA worldGenes & Development, 2009
- 3′ End Processing of a Long Nuclear-Retained Noncoding RNA Yields a tRNA-like Cytoplasmic RNACell, 2008
- Analysis of Turnover and Translation Regulatory RNA-Binding Protein Expression through Binding to Cognate mRNAsMolecular and Cellular Biology, 2007
- Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomasHepatology, 2006