Project description:Background:Long noncoding RNAs (lncRNAs) play important roles in the development and pathophysiology of colorectal cancer (CRC). Our previous study showed that Hes1 was involved in the self-renewal and tumorigenicity of stem-like cancer cells in CRC. Methods:ArrayStar Human LncRNA/mRNA Expression Microarray Version 3.0 was used to detect lncRNA expression in CRC tissues compared with their matched non-tumoral tissues. RNA-binding protein immunoprecipitation and sequencing (RIP-seq) assay was used to detect lncRNAs binding to Hes1. Real-time qPCR was used to detect expression of specific lncRNAs in CRC tissues. Results:We found significantly up-regulated as well as down-regulated lncRNAs in CRC tissues compared with their matched non-tumoral tissues. We also screened a number of lncRNAs interacting with Hes1 in CRC cells. Interestingly, we found several lncRNAs binding to Hes1 (such as, GNAS-AS1, RP11-89K10.1, and RP11-465L10.10) were up-regulated in CRC tissues showed by the tissue microarray. Next, we confirmed that Hes1 directly interacted with these lncRNAs using RIP-qPCR and RNA pulldown assay. Finally, we verified the expression of these lncRNAs in 32 CRC samples as well as the adjacent non-tumoral tissues using real-time qPCR. Conclusions:Based on these, we speculate that Hes1 interacts with one or more lncRNAs which contribute to the development and progression of CRC.
Project description:Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Despite substantial progress in understanding the molecular mechanisms and treatment of CRC in recent years, the overall survival rate of CRC patients has not improved dramatically. The development of CRC is multifactor and multistep processes, in which abnormal gene expression may play an important role. With the advance of human tumor molecular biology, a series of studies have highlighted the role of long non-coding RNAs (lncRNAs) in the development of CRC. CRC-related lncRNAs have been demonstrated to regulate the genes by various mechanisms, including epigenetic modifications, lncRNA-miRNA and lncRNA-protein interactions, and by their actions as miRNA precursors or pseudogenes. Since some lncRNAs can be detected in human body fluid and have good specificity and accessibility, they have been suggested to be used as novel potential biomarkers for CRC diagnosis and prognosis as well as in the prediction of the response to therapy. Therefore, in this review, we will focus on lncRNAs in CRC development, the mechanisms and biomarkers of lncRNAs in CRC.
Project description:Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Despite the advances in the knowledge of pathogenetic molecular mechanisms and the implementation of more effective drug treatments in recent years, the overall survival rate of patients remains unsatisfactory. The high death rate is mainly due to metastasis of cancer in about half of the cancer patients and the emergence of drug-resistant populations of cancer cells. Improved understanding of cancer molecular biology has highlighted the role of non-coding RNAs (ncRNAs) in colorectal cancer development and evolution. ncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions of long non-coding RNAs (lncRNAs) with both microRNAs (miRNAs) and proteins, and through the action of lncRNAs as miRNA precursors or pseudogenes. LncRNAs can also be detected in the blood and circulating ncRNAs have become a new source of non-invasive cancer biomarkers for the diagnosis and prognosis of colorectal cancer, as well as for predicting the response to drug therapy. In this review, we focus on the role of lncRNAs in colorectal cancer development, progression, and chemoresistance, and as possible therapeutic targets.
Project description:Colorectal cancer (CRC) is a common gastrointestinal cancer, with a high incidence and high mortality. Long non-coding RNAs (lncRNAs) are involved in the development, invasion and metastasis, early diagnosis, prognosis, the chemoresistance and radioresistance of CRC through interference with mRNA activity, directly combining with proteins to regulate their activity or alter their localization, influencing downstream gene expression by inhibiting RNA polymerase and regulating gene expression as competing endogenous RNAs. Recent progress in next generation sequencing and transcriptome analysis has revealed that tissue and cancer-type specific lncRNAs could be useful prognostic markers. Here, the CRC-associated lncRNAs from recent studies until October 2016 are reviewed and multiple studies that have confirmed CRC-associated lncRNAs are summarized. This review may be helpful in understanding the overall relationships between the lncRNAs involved in CRC.
Project description:Colorectal cancer (CRC) is the third most prevalent malignant neoplasm worldwide. Recently, in terms of the mechanism of CRC, most studies have focused on protein-coding genes. However, studies have increasingly shown that long non-coding RNAs (lncRNAs) play crucial roles in the proliferation and metastasis of CRC. Investigating this molecular mechanism may provide potential diagnostic tools and therapeutic targets for CRC. This review closely examines the dysregulation of lncRNAs in CRC. On account of different mechanisms being involved in the occurrence and development of CRC, there are several categories of lncRNAs, including lncRNAs related to the Wnt/β-catenin pathway, epithelial mesenchymal transition, epigenetic regulation, angiopoiesis, and chemoresistance. This review summarizes lncRNAs related to the progression of CRC, which may provide insight into the mechanisms and potential markers for prognostic prediction and monitoring relapse of CRC.
Project description:Accumulating evidence highlights the role of long non-coding RNAs (lncRNAs) in tumors. However, the genome-wide expression and roles of lncRNAs in colorectal cancer (CRC) remain unknown. Here, we systematically examined the global gene expressions in primary and synchronous liver metastases CRC tissue, in which thousands of aberrantly expressed lncRNAs were characterized. Co-expression analysis revealed that some lncRNAs correlated to their neighboring mRNAs in expression levels, whereas others formed networks with protein-coding genes in trans. We observed H3K4me3 was enriched at expressed lncRNA transcription start sites (TSSs) and correlated to dysregulated lncRNAs. Furthermore, we identified primary and metastasis tumor linked lncRNA signatures positively correlated with poor-prognosis gene set. Finally, functional experiments demonstrated two candidate lncRNAs were required for proliferation and migration of CRC cells. In summary, we provided a new framework for lncRNA associated clinical prognosis evaluation and target selection of gene therapy in CRC.
Project description:Identification of the colorectal adenoma-carcinoma sequence with its corresponding genetic and epigenetic alterations has significantly increased our knowledge of the etiopathogenesis of colorectal cancer (CRC). However, the molecular mechanisms of colorectal carcinogenesis and metastasis haven't been clearly elucidated. Long non-coding ribonucleic acids (lncRNAs) are key participants of gene regulations rather than "noises". Accumulative studies have implicated that the aberrant expressions of lncRNAs are tightly corelated to CRC screening, diagnosis, prognosis and therapeutic outcomes. Our review focuses on recent findings on the involvement of lncRNAs in CRC oncogenesis and the lncRNA-based clinical implications in patients with CRC.