Abstract
The vital roles of long noncoding RNAs (lncRNAs) have been implicated in growing number of studies in tumor development. LncRNA CCAT1 has been recognized as associated with tumor development, yet its relation with colorectal cancer (CRC) remains elusive. Our study aimed at elucidating the function and mechanisms of long non-coding RNA CCAT1 in CRC. From a lncRNA profile dataset of 38 pairs of matched tumor-control colon tissues from colorectal patients housed in The Cancer Genome Atlas (TCGA), we detected 10 upregulated and 10 down-regulated lncRNAs in CRC. Fifty cases of CRC patients were enrolled to analyze the correlation between the expression of CCAT1 and clinical pathology. The inverse correlation of expression and target relationship between CCAT1 and miR-181a-5p were verified using qRT-PCR and dual-luciferase reporter gene assay. Cell viability, colony formation ability, aggression and apoptosis were determined by MTT assay, colony formation assay, Transwell and wound healing assays and flow cytometry analysis. Furthermore, Xenograft model was used to show that knockdown of CCAT1 inhibits tumor growth in vivo. The expression of lncRNA CCAT1 was significantly upregulated in CRC tissues. The CCAT1 expression was positively associated with cancer stage (American Joint Committee on Cancer stage, P<0.05). CCAT1 promoted cell proliferation, growth and mobility by targeting miR-181a-5p and the silence of CCAT1 increased the cell apoptosis. Same effect was observed in an in vivo xenograft model, which the tumor size and pro-tumor proteins were significantly diminished by knocking down of CCAT1.
Highlights
Colorectal cancer (CRC) is the third most fatal malignant neoplasm worldwide [1]
Our study demonstrated that Long noncoding RNAs (lncRNAs) cancer-associated transcript-1 (CCAT1) could regulate the progression of CRC via down-regulating the expression levels of miR-181a-5p
A total of 178 upregulated lncRNAs and 141 downregulated lncRNAs were identified in 38 pairs CRC tissues
Summary
Colorectal cancer (CRC) is the third most fatal malignant neoplasm worldwide [1]. Research has been done and genetic or epigenetic abnormalities have been related to CRC tumorigenesis and progression [2]. Tumor progression and metastasis are the main cause of death in CRC patients, especially in those at later stages. Despite continuous improvement in diagnostic and medical techniques with various anti-cancer drugs, the overall survival of CRC patients remains comparatively low. Many lncRNAs are shown to regulate the progression of important tumors, including the ability of proliferation, apoptosis, metastasis, senescence, metabolism and drug-resistance [4]. A number of lncRNAs have been functionally www.aging-us.com denominated, a majority of them remain unrecognized and warrant further research
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