Abstract
Gallbladder cancer (GBC) is the most common type of biliary tract cancer worldwide. Long noncoding RNAs (lncRNAs) play essential roles in physiological and pathological development. LncRNA MEG3, a tumor suppressor, has been reported to play important roles in some cancers, but the role of MEG3 in GBC remains largely unknown. The purpose of the present study was to explore the role of MEG3 in proliferation and invasion and the potential molecular mechanism in GBC. We found that MEG3 was downregulated in GBC tissues and cells, and low expression of MEG3 was correlated with poor prognostic outcomes in patients. Overexpression of MEG3 inhibited GBC cell proliferation and invasion, induced cell apoptosis and decreased tumorigenicity in nude mice. Moreover, we found that MEG3 was associated with EZH2 and attenuated EZH2 by promoting its ubiquitination. Furthermore, MEG3 executed its functions via EZH2 to regulate the downstream target gene LATS2. Taken together, these findings suggest that MEG3 is an effective target for GBC therapy and may facilitate the development of lncRNA-directed diagnostics and therapeutics against GBC.
Highlights
Gallbladder cancer (GBC) is the most common type of biliary tract cancer worldwide[1]
Maternally Expressed Gene 3 (MEG3) was downregulated in GBC tissues, and its low expression was associated with poor prognosis of GBC To investigate the expression of MEG3 in GBC tissues and normal tissues, we assessed the MEG3 levels in 50 pairs of GBC tissues and adjacent nontumor tissues by qRT-PCR
QRT-PCR was performed to detect whether MEG3 overexpression had effects on these potential target genes, and we found that only the transcript levels of Large Tumor Suppressor 2 (LATS2) were increased in NOZ cells transfected with the MEG3 plasmid
Summary
Gallbladder cancer (GBC) is the most common type of biliary tract cancer worldwide[1]. Despite the current advances in surgical therapy and chemotherapy for GBC, the overall 5-year survival rate for patients remains less than 5%2. Due to the rapid development of tumor biology and sequencing techniques, molecular pathogenesis has recently been recognized deeply for GBC4 LncRNAs are a class of noncoding transcripts longer than 200 nucleotides that play essential roles in physiological and pathological development. The lncRNA HOTAIR plays important roles in tamoxifen resistance in breast cancer[7]; the lncRNA CAI2 contributes to the paradoxical overexpression of p16 and is associated with poor clinical outcomes in neuroblastoma[8]; and lncRNA PCAT-1 decreases the tumor suppressor BRCA2 in prostate cancer[9].
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