Abstract
BackgroundAccumulated studies indicate that aberrant expression of long noncoding RNAs (lncRNAs) is associated with tumorigenesis and progression of colon cancer. In the present study, long intergenic non-protein coding RNA 1287 (LINC01287) was identified to up-regulate in colon cancer by transcriptome RNA-sequencing, but the exact function remained unclear.MethodsTranscriptome RNA-sequencing was conducted to identify dysregulated lncRNAs. Expression of LINC01287 was evaluated by real-time quantitative PCR. The downstream targets of LINC01287 and miR-4500 were verified by luciferase reporter assay, pull down assay and western blot. The potential functions of LINC01287 were evaluated by cell viability assay, colony formation assay, soft agar assay, flow cytometry, transwell migration and invasion assay, and tumor xenograft growth in colon cancer cells.ResultsOur results indicated that LINC01287 was up-regulated in colon cancer patients. High LINC01287 expression was associated with advanced TNM stage, lymph node metastasis, distant metastasis and shorter overall survival. Knockdown of LINC01287 inhibited cell growth, colony formation in plates and soft agar, transwell cell migration and invasion, and epithelial-mesenchymal transition (EMT) of colon cancer cells, while LINC01287 overexpression had contrary effects. In addition, LINC01287 mediated MAP3K13 expression by sponging miR-4500, thus promoted NF-κB p65 phosphorylation. Restored MAP3K13 expression or miR-4500 knockdown partially abrogated the effects of silencing LINC01287 in colon cancer cells.ConclusionOur findings demonstrated that the LINC01287/miR-4500/MAP3K13 axis promoted progression of colon cancer. Therefore, LINC01287 might be a potential therapeutic target and prognostic marker for colon cancer patients.
Highlights
Accumulated studies indicate that aberrant expression of long noncoding RNAs is associated with tumorigenesis and progression of colon cancer
LINC01287 is up-regulated in colon cancer tissues and closely associated with poor prognosis In order to explore novel genes associated with colon cancer progression, we performed transcriptome RNAsequencing analysis of 4 colon cancer tissues and paired adjacent normal samples
Dysregulation of CRNDE, PVT1, LINC00152, H19, LEF1-AS1, MEG3 and XIST were proved to involve in the initiation, progression, metastasis and chemoresistance of colon cancer cells, indicating that our transcriptome RNA-sequencing was successful and feasible to explore long noncoding RNAs (lncRNAs) playing a role in colon cancer tumorigenesis [22,23,24,25]
Summary
Accumulated studies indicate that aberrant expression of long noncoding RNAs (lncRNAs) is associated with tumorigenesis and progression of colon cancer. Long intergenic non-protein coding RNA 1287 (LINC01287) was identified to up-regulate in colon cancer by transcriptome RNA-sequencing, but the exact function remained unclear. Colon cancer cases are rapidly increased in Asian-Pacific region, mainly ascribed to the growing industrialization and urbanization [3]. Current therapeutic strategies such as chemotherapy, targeted therapy, and immunotherapy achieve marked improvements in the past decades, the prognosis for colon cancer patients remains poor due to late diagnosis and lack of screening methods [4, 5]. Efforts in resolving these issues would obtain a better understanding of this lethal disease and facilitate development of new effective prognostic biomarkers or therapeutic targets for colon cancer
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