Abstract
BackgroundAccumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC.MethodsQuantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1.ResultsHere we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it.ConclusionsOur results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC.
Highlights
Accumulating evidences show that long noncoding RNAs play essential roles in the development and progression of various malignancies
Deleted in lymphocytic leukemia 1 (DLEU1) expression is up-regulated in human CRC tissues To understand the role of long noncoding RNAs (lncRNA) in colorectal cancer, we first analyzed differentially expressed lncRNAs between colorectal cancer tissues and normal tissues according to a microarray data (GSE70880) [29]
We found that DLEU1 was one of the most up-regulated lncRNAs in CRC tissues according to this dataset (Fig. 1a)
Summary
Accumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. Their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). The main cause is the increasing resistance to many anti-cancer agents in most CRC patients [6]. Recent evidence demonstrates that nearly 98% of the genome transcripts in human are noncoding RNAs (ncRNA) [9, 10], among which long noncoding RNAs (lncRNAs) are transcripts of longer than 200 nucleotides and have no protein coding potential [11, 12]. The roles of DLEU1 in other tumors including colorectal cancer remain elusive
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