Abstract
Aim Colon cancer-associated transcript-1 (CCAT1), located in the vicinity of transcription factor c-Myc, was first identified in colon cancer. A small-molecule compound CX3543 (Quarfloxin) selectively targeting Myc G-quadruplexes has entered phase II clinical trials for neuroendocrine carcinomas. The aim of the study was to explore the relationship between CX3543, CCAT1, and cell apoptosis in colon cancer cells. Methods Semiquantitative PCR was used to detect the relative expression of CCAT1 in colon cancer (CC) tissues and HT29 cell lines. Real-time PCR (RT-PCR) was also used to investigate the expression of CCAT1 and c-Myc after HT29 cells being treated by CX3543 for 24 h. Cell apoptosis assay and cell proliferation assay were conducted in HT29 cells after being treated by CX3543. Results The results showed that the expression of CCAT1 was remarkably increased in CC tissues and HT29 cells compared to controls. CX3543 treatment reduced the expression of c-Myc and CCAT1 and promoted cell apoptosis and inhibited cell proliferation. After the expression of CCAT1 was inhibited by sh-CCAT1 transfection, the cell apoptosis rate was higher than that of control group. After the cells were treated by CCAT1 overexpression plasmid transfection and CX3543, the cell apoptosis rate was lower than that of control group. In vivo results showed that CX3543 inhibited the xenograft tumor growth of rats through downregulation of CCAT1. Conclusion Our study demonstrated that CX3543 could inhibit the progression of colon cancer by downregulating CCAT1 expression and might be a potential drug for the treatment of colon cancer.
Highlights
Colon cancer (CC) is a common disease affecting over a million people annually worldwide [1]
The results of real-time PCR indicated that expression levels of cancer-associated transcript 1 (CCAT1) in 20 pairs of human CC tissues were significantly upregulated compared to that of the paratumor tissues (p
We have proved that CX3543 could induce cell apoptosis, and we inferred that CX3543 may induce cell apoptosis through decreasing the expression of CCAT1
Summary
Colon cancer (CC) is a common disease affecting over a million people annually worldwide [1]. Its mortality rate is the third highest among all cancers, leading to approximately 0.6 million deaths annually [2]. It becomes urgent to study the pathogenesis and identify effective risk factors and therapeutic targets of colon cancer. It is found that long noncoding RNAs (LncRNAs) are closely associated with the carcinogenesis and development of tumor. Colon cancer-associated transcript 1 (CCAT1) is a 2628 bp nucleotide-long, noncoding RNA that maps to chromosome 8q24.21, and was first found to be upregulated in colon cancer [3]. CCAT1 is located in the vicinity of c-Myc, a well-known transcription factor [4]
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