Dataset Information

CCAT 1- A Pivotal Oncogenic Long Non-Coding RNA in Colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) is ranked as the third most common cancer and second deadliest cancer in both men and women in the world. Currently, the cure rate and 5-year survival rate of CRC patients remain relatively low. Therefore, discovering a novel molecular biomarker that can be used to improve CRC screening, diagnosis, prognosis, and treatment would be beneficial. Long non-coding RNA colon cancer-associated transcript 1 (CCAT 1) has been found overexpressed in CRC and is associated with CRC tumorigenesis and treatment outcome. CCAT 1 has a high degree of specificity and sensitivity, it is readily detected in CRC tissues and is significantly overexpressed in both premalignant and malignant CRC tissues. Besides, CCAT 1 is associated with clinical manifestation and advanced features of CRC, such as lymph node metastasis, high tumor node metastasis stage, differentiation, invasion, and distant metastasis. In addition, they can upregulate oncogenic c-MYC and negatively modulate microRNAs via different mechanisms of action. Furthermore, dysregulated CCAT 1 also enhances the chemoresistance in CRC cells while downregulation of them reverses the malignant phenotypes of cancer cells. In brief, CCAT 1 serves as a potential screening, diagnostic and prognostic biomarker in CRC, it also serves as a potential therapeutic marker to treat CRC patients.

SUBMITTER: Liau XL

PROVIDER: S-EPMC10070472 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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CCAT 1- A Pivotal Oncogenic Long Non-Coding RNA in Colorectal Cancer.

Liau Xiew Leng XL Salvamani Shamala S Gunasekaran Baskaran B Chellappan Dinesh Kumar DK Rhodes Anthony A Ulaganathan Vaidehi V Tiong Yee Lian YL

British journal of biomedical science 20230321

Colorectal cancer (CRC) is ranked as the third most common cancer and second deadliest cancer in both men and women in the world. Currently, the cure rate and 5-year survival rate of CRC patients remain relatively low. Therefore, discovering a novel molecular biomarker that can be used to improve CRC screening, diagnosis, prognosis, and treatment would be beneficial. Long non-coding RNA colon cancer-associated transcript 1 (CCAT 1) has been found overexpressed in CRC and is associated with CRC t ...[more]

PMID: 37025163

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Project description:BackgroundSeveral investigations have reported diverse roles of long non-coding RNA (lncRNA) in biological processes, tumor development, and progression of colorectal cancer (CRC). In this study, we investigated the lncRNA AC087388.1 tumorigenic role in CRC cells.MethodsThe CRC tissues were collected at the Reza Radiotherapy and Oncology Center, Mashhad, Iran. The human SW-48 and HT-29 CRC cell lines were obtained from the national cell bank of Iran. The cells were cultured according to ATCC (the American Type Culture Collection) recommendations. Quantitative real-time PCR was applied to assess the RNA expression. ShRNA transfection was done to downregulate the target gene. MTT and apoptosis assays were conducted to evaluate cell proliferation and viability, respectively. Colony formation assay, wound healing assay, and invasion assay were applied to determine growth, motility, and invasion of the cells, respectively. ENCORI online tool was used as downstream enrichment analysis.ResultsForty CRC patients were encompassed in this study. The results demonstrated that the lncRNA SLC16A1-AS1, AC087388.1, and ELFN1-AS1 were significantly overexpressed in the CRC tissues in comparison to their normal counterpart margins. All the lncRNAs have shown significant Area Under Curve (AUC) values in the patients. Downregulation of lncRNA AC087388.1 remarkably decreased the cell proliferation and viability of the CRC cells. In addition, the data demonstrated that the downregulation of lncRNA AC087388.1 significantly suppressed cell growth and colony formation capability in the cells. Also, downregulation of lncRNA AC087388.1 attenuated motility and invasion of CRC cells, and significantly decreased the expression of invasion genes. In-silico functional enrichment analysis indicated that the lncRNA AC087388.1 has contributed to crucial signaling pathways in tumorigenesis such as the p53 and Wnt signaling pathways, apoptosis, and cell cycle.ConclusionsAltogether, we showed that lncRNA AC087388.1 has an oncogenic role in tumorigenesis of CRC, and it can be considered as a novel diagnostic and prognostic biomarker in CRC.

Project description:Over the past few decades, researchers have become aware of the importance of non-coding RNA, which makes up the vast majority of the transcriptome. Long non-coding RNAs (lncRNAs) in turn constitute the largest fraction of non-coding transcripts. Increasing evidence has been found for the crucial roles of lncRNAs in both tissue homeostasis and development, and for their functional contributions to and regulation of the development and progression of various human diseases such as cancers. However, so far, only few findings with regards to functional lncRNAs in cancers have been translated into clinical applications. Based on multiple factors such as binding affinity of miRNAs to their lncRNA sponges, we analyzed the competitive endogenous RNA (ceRNA) network for the colorectal cancer RNA-seq datasets from The Cancer Genome Atlas (TCGA). After performing the ceRNA network construction and survival analysis, the lncRNA KCNQ1OT1 was found to be significantly upregulated in colorectal cancer tissues and associated with the survival of patients. A KCNQ1OT1-related lncRNA-miRNA-mRNA ceRNA network was constructed. A gene set variation analysis (GSVA) indicated that the expression of the KCNQ1OT1 ceRNA network in colorectal cancer tissues and normal tissues were significantly different, not only in the TCGA-COAD dataset but also in three other GEO datasets used as validation. By predicting comprehensive immune cell subsets from gene expression data, in samples grouped by differential expression levels of the KCNQ1OT1 ceRNA network in a cohort of patients, we found that CD4+, CD8+, and cytotoxic T cells and 14 other immune cell subsets were at different levels in the high- and low-KCNQ1OT1 ceRNA network score groups. These results indicated that the KCNQ1OT1 ceRNA network could be involved in the regulation of the tumor microenvironment, which would provide the rationale to further exploit KCNQ1OT1 as a possible functional contributor to and therapeutic target for colorectal cancer.

Dataset Information

CCAT 1- A Pivotal Oncogenic Long Non-Coding RNA in Colorectal Cancer.

Publications

CCAT 1- A Pivotal Oncogenic Long Non-Coding RNA in Colorectal Cancer.

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