Abstract
BackgroundGallbladder cancer (GBC) is the most malignant cancer occurring in the biliary tract cancer featured with undesirable prognosis, in which most patients die within a year of cholecystectomy. Long noncoding RNAs (lncRNAs) function as critical regulators of multiple stages of cancers. Herein, the mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in GBC is investigated.MethodsMicroarray-based analysis initially provided data suggesting that the expression of MALAT1 was up-regulated while that of the ABI family member 3 binding protein (ABI3BP) was down-regulated in GBC tissues and cell lines. Kaplan-Meier method was then adopted to analyze the relationship between the MALAT1 expression and overall survival and disease-free survival of patients with GBC. A set of in vitro and in vivo experiments were conducted by transducing ABI3BP-vector or sh-MALAT1 into GBC cells.ResultsThe results confirmed that the cancer prevention effects triggered by restored ABI3BP and depleted MALAT1 as evidenced by suppressed cell growth and enhanced cell senescence. MALAT1 was observed to down-regulate ABI3BP expression through recruitment of the enhancer of zeste homolog 2 (EZH2) to the ABI3BP promoter region while the silencing of MALAT1 or suppression of H3K27 methylation was observed to promote the expression of ABI3BP. Furthermore, GBC patients with high expression of MALAT1 indicated poor prognosis.ConclusionThe current study clarifies that MALAT1 silencing and ABI3BP elevation impede the GBC development through the H3K27 methylation suppression induced by EZH2, highlighting a promising competitive paradigm for therapeutic approaches of GBC.
Highlights
Gallbladder cancer (GBC) is the most malignant cancer occurring in the biliary tract cancer featured with undesirable prognosis, in which most patients die within a year of cholecystectomy
In an attempt to investigate the effects of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) on the GBC cell lines, selected cell line was analyzed in subsequent experiments
The results obtained revealed that the expression of MALAT1 in GBC-SD, SGC-996, NOZ, OCUG1 cells was significantly elevated when compared to the human gallbladder epithelial cells (HGBECs)
Summary
Gallbladder cancer (GBC) is the most malignant cancer occurring in the biliary tract cancer featured with undesirable prognosis, in which most patients die within a year of cholecystectomy. The mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in GBC is investigated. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs), such as lncRNA KIAA0125, lncRNA GCASPC and lncRNA H19, serve as key regulators in the biological functions of GBC cells [4,5,6]. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) represents a novel lncRNA localized in human chromosome 11q13, which is expressed in abundance in various mammalian species, from a physiological and pathophysiological perspective [7]. A previous study demonstrated the ability of ABI3BP to serve as a regulator of cardiac progenitor cell proliferation and differentiation [12]. The aim of the current study was to investigate the mechanism by which MALAT1 and ABI3BP influence GBC, in an attempt to identify a novel diagnostic and prognostic biomarker for better understanding the pathogenesis and treatment of GBC
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