C-Myc-activated long noncoding RNA CCAT1 promotes colon cancer cell proliferation and invasion

Abstract

Recently, more and more evidence are rapidly accumulating that long noncoding RNAs (lncRNAs) are involved in human tumorigenesis and misregulated in many cancers, including colon cancer. LncRNA could regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, which indicates that lncRNA would be valuable biomarkers and therapeutic targets. Colon cancer-associated transcript 1 (CCAT1) is a 2628 nucleotide-lncRNA and located in the vicinity of a well-known transcription factor c-Myc. CCAT1 has been found to be upregulated in many cancers, including gastric carcinoma and colonic adenoma-carcinoma. However, its roles in colon cancer are still not well documented and need to be investigated. In this study, we aim to investigate the prognostic value and biological function of CCAT1 and discover which factors may contribute to the deregulation of CCAT1 in colon cancer. Our results revealed that CCAT1 was significantly overexpressed in colon cancer tissues when compared with normal tissues, and its increased expression was correlated with patients' clinical stage, lymph nodes metastasis, and survival time after surgery. Moreover, c-Myc could promote CCAT1 transcription by directly binding to its promoter region, and upregulation of CCAT1 expression in colon cancer cells promoted cell proliferation and invasion. These data suggest that c-Myc-activated lncRNA CCAT1 expression contribute to colon cancer tumorigenesis and the metastatic process and could predict the clinical outcome of colon cancer and be a potential target for lncRNA direct therapy.

Long non-coding RNA colon cancer–associated transcript 1 functions as a competing endogenous RNA to regulate cyclin-dependent kinase 1 expression by sponging miR-490-3p in hepatocellular carcinoma progression

“…3,4 Colon cancer-associated transcript 1 (CCAT1), a ~2-kb lncRNA located at chromosome 8q24.21, is first found to be upregulated in colon cancer. 5 Recently, some reports have found that CCAT1 is involved in tumor progression and tumorigenesis in various types of cancers including colon cancer, 6 gastric cancer, 7 and colorectal cancer. 8 The competitive endogenous RNA (ceRNA) mechanism for CCAT1 and microRNAs involving in tumor progression has been reported in some studies, for example, Zhou et al 9 reported the lncRNA CCAT1/miR-490 axis regulated gastric cancer cell migration by targeting hnRNPA1.…”

A potential biomarker for colorectal cancer: long non-coding RNA RP1-13P20.6

“…As examples, lncRNAs such as CCAT1 [24][25], CCAT2 [26], HOTAIR [27] and MALAT1 [28] are increased in CRC tissues compared to NATs and have been identified as oncogenes. The lncRNAs can regulate the expression of their target genes, activate some signaling pathways, and promote cell proliferation, metastasis, and tumor recurrence [29][30][31][32]. However, lncRNAs such as MEG3, FER1L4 and ncRAN are downregulated in both cancerous tissues and cell lines [33][34][35].…”

Long non-coding RNA CCAT1 is overexpressed in oral squamous cell carcinomas and predicts poor prognosis

“…The CCAT1 locus has been presented to harbor a super-enhancer that could control the c-Myc expression. The CCAT1 was demonstrated to interact with a transcriptional enhancer MYC-335 via chromatin looping and consequently, could interact with the MYC-promoter resulting regulation of c-Myc expression in cis (10,27). In addition, knockdown of CCAT1 led to a decrease in c-Myc levels in colon cancer-derived cell lines (28).…”

“…Previous studies have indicated that CCAT1 is differentially expressed in several types of cancers, including colon cancer, gastric cancer, gall bladder cancer and hepatocellular carcinoma (7)(8)(9). The CCAT1 was identified to be significantly overexpressed and clinically correlated with colon cancer patients' disease stage, lymph node metastasis and survival after surgery (10). In addition, CCAT1 was demonstrated to correlate with overall survival and progression-free survival in breast cancer (11).…”