Abstract
BackgroundThe long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC). However, its underlying mechanisms in the progression of CRC have not been well studied.MethodsTo investigate the clinical significance of NEAT1, we analyzed its expression levels in a publicly available dataset and in 71 CRC samples from Fudan University Shanghai Cancer Center. Functional assays, including the CCK8, EdU, colony formation, wound healing, and Transwell assays, were used to determine the oncogenic role of NEAT1 in human CRC progression. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and Dual-Luciferase Reporter Assays were used to determine the mechanism of NEAT1 in CRC progression. Animal experiments were used to determine the role of NEAT1 in CRC tumorigenicity and metastasis in vivo.ResultsNEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues. Altered NEAT1 expression led to marked changes in proliferation, migration, and invasion of CRC cells both in vitro and in vivo. Mechanistically, we found that NEAT1 directly bound to the DDX5 protein, regulated its stability, and sequentially activated Wnt signaling. Our study showed that NEAT1 indirectly activated the Wnt/β-catenin signaling pathway via DDX5 and fulfilled its oncogenic functions in a DDX5-mediated manner. Clinically, concomitant NEAT1 and DDX5 protein levels negatively correlated with the overall survival and disease-free survival of CRC patients.ConclusionsOur findings indicated that NEAT1 activated Wnt signaling to promote colorectal cancer progression and metastasis. The NEAT1/DDX5/Wnt/β-catenin axis could be a potential therapeutic target of pharmacological strategies.
Highlights
The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC)
NEAT1 is upregulated in human CRC tissues and is associated with a poor prognosis in CRC patients To investigate the clinical significance of NEAT1, we analyzed its expression levels in the publicly available TCGA dataset and in data from 71 CRC samples from Fudan University Shanghai Cancer Center (FDUSCC)
Our results revealed that patients with high NEAT1 expression showed obviously poorer
Summary
The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC). Its underlying mechanisms in the progression of CRC have not been well studied. Long noncoding RNAs (lncRNAs) are defined as RNA polymerase II transcripts longer than 200 nucleotides in length that lack a significant protein-coding capacity [3, 4]. Over the past two decades, the biogenesis and functional mechanisms of miRNAs have been extensively elucidated. LncRNAs have a great biological significance in the occurrence and progression of cancers because they can interact with cancer stem cells and affect cancer metastasis and recurrence [5]. As expected, increasing evidence suggests that many lncRNAs fulfill their functions through specific interactions with other cellular factors (proteins, DNA, and other RNA molecules). Finding lncRNA interacting partners is considered a strategy to gain insights into their molecular mechanisms [6]
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