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Characterizing Colorectal Cancer: MicroRNAs Are Key Molecules Involved in the Gene Regulation Network of Carcinogenesis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (25 September 2021) | Viewed by 11439

Special Issue Editor

Dr. Andrea Angius

E-Mail Website
Guest Editor
Institute of Genetic and Biomedical Research (IRGB), CNR, Cittadella Universitaria di Cagliari, 09042 Monserrato, Italy
Interests: cancer genetics; colorectal cancer; miRNA; RNA-seq and single-cell profiling; rare genetic diseases; molecular diagnosis; metabolism; bioinformatics; integrated omics approaches; precision medicine

Special Issue Information

Dear Colleagues,

As is well known, colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract or large intestine and the third leading cause of cancer death worldwide. The development of a non-invasive CRC diagnosis may be a good clue for the management, treatment, and prevention of relapse and/or prognosis of CRC. The development of high-throughput sequencing technologies and bioinformatics prediction methods has greatly enhanced oncologic research on miRNA. These molecules are important regulators of carcinogenesis, progression, invasion, angiogenesis, and metastases in CRC. For this reason, miRNAs can be used as potential biomarkers for diagnosis, prognosis, and treatment, or even just as targets, and could be promising tools to identify specific stages of the tumor.

This Special Issue aims to discuss the staging of CRC versus specific miRNAs particularly on the biogenesis, characteristics, and function of these molecules. We want to dissect the role of microRNAs in different molecular mechanisms and cellular targets involved in their ability to limit and amplify proliferation, cell cycle progression, and apoptosis. MiRNAs may influence a variety of biological cascades regarding the selectivity of genes and target proteins. We want also to consider experimental techniques used for isolation, detection, and bioinformatics algorithms for the target prediction of miRNAs. This issue focuses on both basic science and translational research in order to provide an in-depth picture of the mechanism of action underlying miRNAs to portray their role in tumorigenesis.

Dr. Andrea Angius
Guest Editor

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Keywords

  • cancer genetics
  • colorectal cancer
  • miRNA
  • RNA-seq and single-cell profiling
  • rare genetic diseases
  • molecular diagnosis
  • metabolism
  • bioinformatics
  • integrated omics approaches
  • precision medicine

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Published Papers (3 papers)

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Research

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19 pages, 8788 KiB  
Article
GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model
by Daniela Gerovska, Patricia Garcia-Gallastegi, Olatz Crende, Joana Márquez, Gorka Larrinaga, Maite Unzurrunzaga, Marcos J. Araúzo-Bravo and Iker Badiola
Int. J. Mol. Sci. 2021, 22(9), 4819; https://doi.org/10.3390/ijms22094819 - 1 May 2021
Cited by 7 | Viewed by 3101
Abstract
Cancer is a phenomenon broadly related to ageing in various ways such as cell cycle deregulation, metabolic defects or telomerases dysfunction as principal processes. Although the tumor cell is the main actor in cancer progression, it is not the only element of the [...] Read more.
Cancer is a phenomenon broadly related to ageing in various ways such as cell cycle deregulation, metabolic defects or telomerases dysfunction as principal processes. Although the tumor cell is the main actor in cancer progression, it is not the only element of the disease. Cells and the matrix surrounding the tumor, called the tumor microenvironment (TME), play key roles in cancer progression. Phenotypic changes of the TME are indispensable for disease progression and a few of these transformations are produced by epigenetic changes including miRNA dysregulation. In this study, we found that a specific group of miRNAs in the liver TME produced by colon cancer called geromiRs, which are miRNAs related to the ageing process, are significantly downregulated. The three principal cell types involved in the liver TME, namely, liver sinusoidal endothelial cells, hepatic stellate (Ito) cells and Kupffer cells, were isolated from a murine hepatic metastasis model, and the miRNA and gene expression profiles were studied. From the 115 geromiRs and their associated hallmarks of aging, which we compiled from the literature, 75 were represented in the used microarrays, 26 out of them were downregulated in the TME cells during colon cancer colonization of the liver, and none of them were upregulated. The histone modification hallmark of the downregulated geromiRs is significantly enriched with the geromiRs miR-15a, miR-16, miR-26a, miR-29a, miR-29b and miR-29c. We built a network of all of the geromiRs downregulated in the TME cells and their gene targets from the MirTarBase database, and we analyzed the expression of these geromiR gene targets in the TME. We found that Cercam and Spsb4, identified as prognostic markers in a few cancer types, are associated with downregulated geromiRs and are upregulated in the TME cells. Full article
(This article belongs to the Special Issue Characterizing Colorectal Cancer: MicroRNAs Are Key Molecules Involved in the Gene Regulation Network of Carcinogenesis)
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Review

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17 pages, 1351 KiB  
Review
The Role of miRNAs, miRNA Clusters, and isomiRs in Development of Cancer Stem Cell Populations in Colorectal Cancer
by Victoria A. Stark, Caroline O. B. Facey, Vignesh Viswanathan and Bruce M. Boman
Int. J. Mol. Sci. 2021, 22(3), 1424; https://doi.org/10.3390/ijms22031424 - 31 Jan 2021
Cited by 19 | Viewed by 4324
Abstract
MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) during development and altered expression can cause developmental defects and/or disease. Indeed, aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has been linked to many cancers. Mounting evidence also [...] Read more.
MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) during development and altered expression can cause developmental defects and/or disease. Indeed, aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has been linked to many cancers. Mounting evidence also indicates a role for miRNAs in the development of the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current research on miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentially expressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genes to influence CSC phenotype. Accordingly, we discuss the specific miRNA cluster classifications and isomiRs that are predicted to target the ALDH1, CD166, BMI1, LRIG1, and LGR5 SC genes. miR-23b and miR-92A are of particular interest because our previously reported studies on miRNA expression in isolated normal versus malignant human colonic SCs showed that miR-23b and miR-92a are regulators of the LGR5 and LRIG1 SC genes, respectively. We also identify additional miRNAs whose expression inversely correlated with mRNA levels of their target genes and associated with CRC patient survival. Altogether, our deliberation on miRNAs, their clusters, and isomiRs in regulation of SC genes could provide insight into how dysregulation of miRNAs leads to the emergence of different CSC populations and SC overpopulation in CRC. Full article
(This article belongs to the Special Issue Characterizing Colorectal Cancer: MicroRNAs Are Key Molecules Involved in the Gene Regulation Network of Carcinogenesis)
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12 pages, 1002 KiB  
Review
Epigenetic Aging and Colorectal Cancer: State of the Art and Perspectives for Future Research
by Andrea Maugeri, Martina Barchitta, Roberta Magnano San Lio, Giovanni Li Destri, Antonella Agodi and Guido Basile
Int. J. Mol. Sci. 2021, 22(1), 200; https://doi.org/10.3390/ijms22010200 - 28 Dec 2020
Cited by 7 | Viewed by 3352
Abstract
Although translational research has identified a large number of potential biomarkers involved in colorectal cancer (CRC) carcinogenesis, a better understanding of the molecular pathways associated with biological aging in colorectal cells and tissues is needed. Here, we aim to summarize the state of [...] Read more.
Although translational research has identified a large number of potential biomarkers involved in colorectal cancer (CRC) carcinogenesis, a better understanding of the molecular pathways associated with biological aging in colorectal cells and tissues is needed. Here, we aim to summarize the state of the art about the role of age acceleration, defined as the difference between epigenetic age and chronological age, in the development and progression of CRC. Some studies have shown that accelerated biological aging is positively associated with the risk of cancer and death in general. In line with these findings, other studies have shown how the assessment of epigenetic age in people at risk for CRC could be helpful for monitoring the molecular response to preventive interventions. Moreover, it would be interesting to investigate whether aberrant epigenetic aging could help identify CRC patients with a high risk of recurrence and a worst prognosis, as well as those who respond poorly to treatment. Yet, the application of this novel concept is still in its infancy, and further research should be encouraged in anticipation of future applications in clinical practice. Full article
(This article belongs to the Special Issue Characterizing Colorectal Cancer: MicroRNAs Are Key Molecules Involved in the Gene Regulation Network of Carcinogenesis)
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