Abstract
Introduction: Epigenetic alterations and aberrantly expressed long noncoding RNAs (lncRNAs) are pervasive in colorectal cancer (CRC) tumorigenesis. DNA methylation could control lncRNA expression and play an important role in tumor initiation and progression. However, the DNA methylation that regulates lncRNAs in CRC remains poorly characterized.Materials and Methods: In our research, we integrated dysregulated expression and methylation of lncRNAs between colorectal tumor and adjacent mucosa tissues from The Cancer Genome Atlas database. With the use of this strategy, LINC00460, the most frequently epigenetically activated, was identified and further verified in the Cancer Cell Line Encyclopedia and Gene Expression Omnibus databases.Results: Patients with high expression of LINC00460 are prone to metastasis and are associated with poor prognosis. Abnormally expressed LINC00460 could be used as an independent prognostic risk factor for disease-free survival. Knockdown of LINC00460 promotes colon cancer cell invasion and migration in vitro.Conclusion: In summary, our results suggest that DNA methylation-regulated LINC00460 could promote CRC metastasis and serve as a potential therapeutic target for CRC.
Highlights
Epigenetic alterations and aberrantly expressed long noncoding RNAs are pervasive in colorectal cancer (CRC) tumorigenesis
The CpG islands significantly related to long noncoding RNAs (lncRNAs) expression were filtered out and further verified in the GEO database
To identify the differential expressed lncRNAs between CRC and normal tissues, we analyzed the TCGA database and screened 75 differently expressed (71 upregulated and 4 downregulated) lncRNAs according to the criteria (Figure 1A and Supplementary Table 1)
Summary
Epigenetic alterations and aberrantly expressed long noncoding RNAs (lncRNAs) are pervasive in colorectal cancer (CRC) tumorigenesis. DNA methylation could control lncRNA expression and play an important role in tumor initiation and progression. The DNA methylation that regulates lncRNAs in CRC remains poorly characterized. The combination of chemotherapy regimens and targeted therapies has prominently improved the survival rate for patients with metastasis; the 5-year survival rate remains below 15% (Brenner et al, 2014). The aberrant expression of long noncoding RNAs (lncRNAs) plays critical roles in multiple biological processes of CRC, such as tumorigenesis, proliferation, and metastasis (Ragusa et al, 2015; Weng et al, 2016). Similar to protein-coding genes, lncRNA expression is subject to changes, such as copy-number alterations (Hu et al, 2014), cancer risk polymorphism
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