Noncoding RNAs in inflammation and colorectal cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Ma S
PROVIDER: S-EPMC7567496 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Colorectal cancer (CRC) is one of the most common cancers in humans and a leading cause of cancer-related deaths worldwide. As in the case of other cancers, CRC heterogeneity leads to a wide range of clinical outcomes and complicates therapy. Over the years, multiple factors have emerged as markers of CRC heterogeneity, improving tumor classification and selection of therapeutic strategies. Understanding the molecular mechanisms underlying this heterogeneity remains a major challenge. A considerable research effort is therefore devoted to identifying additional features of colorectal tumors, in order to better understand CRC etiology and to multiply therapeutic avenues. Recently, long noncoding RNAs (lncRNAs) have emerged as important players in physiological and pathological processes, including CRC. Here we looked for lncRNAs that might contribute to the various colorectal tumor phenotypes. We thus monitored the expression of 4898 lncRNA genes across 566 CRC samples and identified 282 lncRNAs reflecting CRC heterogeneity. We then inferred potential functions of these lncRNAs. Our results highlight lncRNAs that may participate in the major processes altered in distinct CRC cases, such as WNT/?-catenin and TGF-? signaling, immunity, the epithelial-to-mesenchymal transition (EMT), and angiogenesis. For several candidates, we provide experimental evidence supporting our functional predictions that they may be involved in the cell cycle or the EMT. Overall, our work identifies lncRNAs associated with key CRC characteristics and provides insights into their respective functions. Our findings constitute a further step towards understanding the contribution of lncRNAs to CRC heterogeneity. They may open new therapeutic opportunities.
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Project description:Noncoding RNAs (ncRNAs) represent a class of RNA molecules that typically do not code for proteins. Emerging data suggest that ncRNAs play an important role in several physiological and pathological conditions such as cancer. The best-characterized ncRNAs are the microRNAs (miRNAs), which are short, approximately 22-nucleotide sequences of RNA of approximately 22-nucleotide in length that regulate gene expression at the posttranscriptional level, through transcript degradation or translational repression. MiRNAs can function as master gene regulators, impacting a variety of cellular pathways important to normal cellular functions as well as cancer development and progression. In addition to miRNAs, long ncRNAs, which are transcripts longer than 200 nucleotides, have recently emerged as novel drivers of tumorigenesis. However, the molecular mechanisms of their regulation and function, and the significance of other ncRNAs such as piwi-interacting RNAs in pancreas carcinogenesis are largely unknown. This review summarizes the growing body of evidence supporting the vital roles of ncRNAs in pancreatic cancer, focusing on their dysregulation through both genetic and epigenetic mechanisms, and highlighting the promise of ncRNAs in diagnostic and therapeutic applications of pancreatic cancer.
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Project description:Colorectal cancer is the third most common form of cancer in developed countries and, despite the improvements achieved in its treatment options, remains as one of the main causes of cancer-related death. In this review, we first focus on colorectal carcinogenesis and on the genetic and epigenetic alterations involved. In addition, noncoding RNAs have been shown to be important regulators of gene expression. We present a general overview of what is known about these molecules and their role and dysregulation in cancer, with a special focus on the biogenesis, characteristics, and function of microRNAs. These molecules are important regulators of carcinogenesis, progression, invasion, angiogenesis, and metastases in cancer, including colorectal cancer. For this reason, miRNAs can be used as potential biomarkers for diagnosis, prognosis, and efficacy of chemotherapeutic treatments, or even as therapeutic agents, or as targets by themselves. Thus, this review highlights the importance of miRNAs in the development, progression, diagnosis, and therapy of colorectal cancer and summarizes current therapeutic approaches for the treatment of colorectal cancer.
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Project description:Long noncoding RNAs are non-protein coding transcripts longer than 200 nucleotides in length. By the advance in genetic and bioinformatic technologies, the new genomic landscape including noncoding transcripts has been revealed. Despite their non-capacity to be translated into proteins, lncRNAs have a versatile functions through various mechanisms interacting with other cellular molecules including DNA, protein, and RNA. Recent research interest and endeavor have identified the functional role of lncRNAs in various diseases including cancer. Colorectal cancer (CRC) is not only one of the most frequent cancer but also one of the cancer types with remarkable achievements in lncRNA research. Of the numerous notable lncRNAs identified and characterized in CRC, we will focus on key lncRNAs with the high potential as CRC-specific biomarkers in this review.
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Project description:Colorectal cancer (CRC) is one of the most common types of human cancers. However, the mechanisms underlying CRC progression remained elusive. This study identified differently expressed messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and small nucleolar RNAs (snoRNAs) between pre-therapeutic biopsies and post-therapeutic resections of locally advanced CRC by analyzing a public dataset, GSE94104. We identified 427 dysregulated mRNAs, 4 dysregulated lncRNAs, and 19 dysregulated snoRNAs between pre- and post-therapeutic locally advanced CRC samples. By constructing a protein-protein interaction network and co-expressing networks, we identified 10 key mRNAs, 4 key lncRNAs, and 7 key snoRNAs. Bioinformatics analysis showed therapy-related mRNAs were associated with nucleosome assembly, chromatin silencing at recombinant DNA, negative regulation of gene expression, and DNA replication. Therapy-related lncRNAs were associated with cell adhesion, extracellular matrix organization, angiogenesis, and sister chromatid cohesion. In addition, therapy-related snoRNAs were associated with DNA replication, nucleosome assembly, and telomere organization. We thought this study provided useful information for identifying novel biomarkers for CRC.
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Project description:The mammalian transcriptome has recently been revealed to encompass a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. MicroRNAs (miRNAs), the best studied of the short noncoding RNAs (sncRNAs), have been extensively characterized with regard to their biogenesis, function and importance in tumorigenesis. Another class of sncRNAs called piwi-interacting RNAs (piRNAs) has also gained attention recently in cancer research owing to their critical role in stem cell regulation. Long noncoding RNAs (lncRNAs) of >200 nucleotides in length have recently emerged as key regulators of developmental processes, including mammary gland development. lncRNA dysregulation has also been implicated in the development of various cancers, including breast cancer. In this review, we describe and discuss the roles of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the initiation and progression of breast tumorigenesis, with a focus on outlining the molecular mechanisms of oncogenic and tumor-suppressor ncRNAs. Moreover, the current and potential future applications of ncRNAs to clinical breast cancer research are also discussed, with an emphasis on ncRNA-based diagnosis, prognosis and future therapeutics.
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Project description:Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, causing a large number of cancer-related deaths each year. Patients are usually diagnosed at advanced and incurable stages due to the lack of suitable screening methods for early detection. Noncoding RNAs (ncRNAs), including small and long noncoding RNAs (lncRNA), are known to have significant regulatory functions, and accumulating evidence suggests that circulating ncRNAs have potential applications as noninvasive biomarkers for diagnosing CRC, evaluating its prognosis, or predicting chemosensitivity in the general population. In this review, we summarize the origins of circulating ncRNAs and provide details of single and multiple circulating ncRNAs that might have roles as diagnostic and prognostic biomarkers in CRC. We end by discussing circulating ncRNAs that may distinguish patients with resistance to chemotherapy.
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Project description:Colorectal cancer (CRC) is the third leading cause of death worldwide, comprising nearly 8% of cancer-related deaths per year. In South Korea, for example, CRC is the second most common cancer in men, and third in women. This study reports on the association of CRC with genetic variations in long noncoding RNAs, activators, and inhibitors of a cell proliferation pathway. Five normal colon mucosa tissue samples and their matched five-stage IV CRC samples were evaluated (dataset Gene Expression Omnibus accession: GSE50760). We identified more than 5000 differentially expressed genes (DEGs). The Wnt pathway had the greatest portion of DEGs, including activators, inhibitors, and associated long noncoding RNAs (lncRNAs), suggesting the importance of Wnt pathway in CRC. The following genes were aberrantly expressed: WIF1, SFRP4, CD82, WNT2, WNT3, WNT5A, HOTAIR, CRNDE, and UCA1. Notably, HOTAIR is known to silence WIF1, and WIF1 inhibits the Wnt ligands to negatively regulate the pathway. The lncRNA CRNDE positively regulates WNT5A, while UCA1 positively regulates WNT2 and WNT3. We note that HOTAIR was unable to silence WIF1. CRNDE and UCA1 were found to be upregulated, which may explain the high expression of the WIF1 targets. Furthermore, 10 single-nucleotide polymorphisms (SNPs) were identified in five of the candidate genes above. A possible novel SNP in CD82, chr11:44619242T > C, was predicted to introduce a ZBTB7A binding site. These SNPs are hypothesized to contribute to aberrant and discrepant regulation of the Wnt pathway in a context of CRC pathogenesis. These findings collectively inform future research on diagnostics and therapeutics innovation in CRC.
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Project description:Genome-wide cancer mutation analyses are revealing an extensive landscape of functional mutations within the noncoding genome, with profound effects on the expression of long noncoding RNAs (lncRNAs). While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, we now understand that lncRNAs drive many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein, and RNA. Recent advancements in surveying lncRNA molecular mechanisms are now providing the tools to functionally annotate these cancer-associated transcripts, making these molecules attractive targets for therapeutic intervention in the fight against cancer.
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