microRNAs in Colorectal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (1 May 2021) | Viewed by 14309

Special Issue Editors


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Guest Editor
Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain
Interests: colorectal cancer; breast cancer; PP2A pathway

E-Mail Website
Guest Editor
1. Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain
2. Medical Oncology Department, University Hospital “Fundación Jiménez Díaz”, UAM, E-28040 Madrid, Spain
Interests: colorectal cancer; PP2A pathway; locally advanced rectal cancer; chemotherapy resistance; microRNAs

Special Issue Information

Dear Colleagues,

Colorectal cancer is the gastrointestinal cancer with the highest incidence and a major cause of cancer-related death worldwide. It is a heterogeneous disease characterized by a progressive accumulation of genetic and epigenetic alterations that drive tumor progression. The subgroup of patients with distant metastases at diagnosis and those who progress to metastatic disease represent a therapeutic challenge due to their very poor outcome. It has been well demonstrated that microRNAs play key regulatory roles in colorectal cancer, emerging as novel biomarkers and promising molecular targets in this disease. However, their clinical and therapeutic impact needs to be further established before their future inclusion in clinical protocols.

This Special Issue will illustrate the clinical and therapeutic significance of microRNA deregulation in colorectal cancer and their crucial contribution to metastatic progression. We welcome works that provide significant advances in this field with a clear translational impact and novelty.

Dr. Ion Cristobal
Dr. Cristina Carames
Guest Editors

Manuscript Submission Information

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Keywords

  • microRNA
  • colorectal cancer
  • biomarker
  • drug resistance
  • progression
  • targeted therapy

Published Papers (6 papers)

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Research

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14 pages, 1414 KiB  
Article
Validation of microRNA-199b as A Promising Predictor of Outcome and Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer Patients
by Ion Cristóbal, Andrea Santos, Jaime Rubio, Cristina Caramés, Sandra Zazo, Marta Sanz-Álvarez, Melani Luque, Juan Madoz-Gúrpide, Federico Rojo and Jesús García-Foncillas
Cancers 2021, 13(19), 5003; https://doi.org/10.3390/cancers13195003 - 5 Oct 2021
Cited by 3 | Viewed by 1628
Abstract
The absence of established predictive markers with value to anticipate response to neoadjuvant 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) represents a current major challenge in locally advanced rectal cancer (LARC). The tumor suppressor microRNA (miR)-199b has been reported to play a key role determining 5-FU [...] Read more.
The absence of established predictive markers with value to anticipate response to neoadjuvant 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) represents a current major challenge in locally advanced rectal cancer (LARC). The tumor suppressor microRNA (miR)-199b has been reported to play a key role determining 5-FU sensitivity of colorectal cancer cells through the regulation of several signaling pathways, and has emerged as a novel molecular target to overcome the 5-FU resistant phenotype. Moreover, miR-199b downregulation was described as a common alteration that predicts lack of response to preoperative CRT in LARC but this issue needs to be confirmed in independent larger cohorts. Here, we evaluate the clinical impact of miR-199b in LARC and perform additional analyses to further clarify its potential relevance as novel marker in this disease. Thus, miR-199b expression was quantified by real-time-PCR in a cohort of 185 LARC patients, observing this miR downregulated in 22.2% of cases and significantly associated with higher tumor size (p = 0.026) and positive lymph node after CRT (p = 0.005), and higher pathological stage (p = 0.004). Notably, this alteration showed a strong independent predictive value of poor pathological response to neoadjuvant CRT (p = 0.004). Moreover, the subgroup of cases with low miR-199b levels had a markedly shorter overall (p < 001) and event-free survival (p < 0.001), and multivariate analyses showed that miR-199b deregulation represents an independent prognosticator for patient outcome in LARC. Interestingly, the prognostic impact of this miR was strongly significant in both younger and elderly patients, and was very effective determining patient recurrence (p = 0.004). Finally, we compared miR-199b expression profiles in a set of cases with pre and post-treatment samples available, observing that only a minimal response leads to miR-199b increase levels, further suggesting its potential clinical and therapeutic relevance as a promising marker and novel molecular target for the management of LARC. Full article
(This article belongs to the Special Issue microRNAs in Colorectal Cancer)
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13 pages, 829 KiB  
Article
Low MicroRNA-19b Expression Shows a Promising Clinical Impact in Locally Advanced Rectal Cancer
by Jaime Rubio, Ion Cristóbal, Andrea Santos, Cristina Caramés, Melani Luque, Marta Sanz-Alvarez, Sandra Zazo, Juan Madoz-Gúrpide, Federico Rojo and Jesús García-Foncillas
Cancers 2021, 13(6), 1456; https://doi.org/10.3390/cancers13061456 - 22 Mar 2021
Cited by 11 | Viewed by 1804
Abstract
The standard treatment for patients with locally advanced colorectal cancer (LARC) is neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy (CRT) followed by surgical mesorectal excision. However, the lack of response to this preoperative treatment strongly compromises patient outcomes and leads to surgical delays and undesired [...] Read more.
The standard treatment for patients with locally advanced colorectal cancer (LARC) is neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy (CRT) followed by surgical mesorectal excision. However, the lack of response to this preoperative treatment strongly compromises patient outcomes and leads to surgical delays and undesired toxicities in those non-responder cases. Thus, the identification of effective and robust biomarkers to predict response to preoperative CRT represents an urgent need in the current clinical management of LARC. The oncomiR microRNA-19b (miR-19b) has been reported to functionally play oncogenic roles in colorectal cancer (CRC) cells as well as regulate 5-FU sensitivity and determine outcome in CRC patients. However, its clinical impact in LARC has not been previously investigated. Here, we show that miR-19b deregulation is a common event in this disease, and its decreased expression significantly associates with lower tumor size after CRT (p = 0.003), early pathological stage (p = 0.003), and absence of recurrence (p = 0.001) in LARC patients. Interestingly, low miR-19b expression shows a predictive value of better response to neoajuvant CRT (p < 0.001), and the subgroup of LARC patients with low miR-19b levels have a markedly longer overall (p = 0.003) and event-free survival (p = 0.023). Finally, multivariate analyses determined that miR-19b independently predicts both patient outcome and response to preoperative CRT, highlighting its potential clinical usefulness in the management of LARC patients. Full article
(This article belongs to the Special Issue microRNAs in Colorectal Cancer)
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21 pages, 3818 KiB  
Article
MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion
by Tana Machackova, Petra Vychytilova-Faltejskova, Kamila Souckova, Karolina Trachtova, Dominika Brchnelova, Marek Svoboda, Igor Kiss, Vladimir Prochazka, Zdenek Kala and Ondrej Slaby
Cancers 2020, 12(12), 3518; https://doi.org/10.3390/cancers12123518 - 26 Nov 2020
Cited by 36 | Viewed by 3018
Abstract
Background: Growing evidence suggests that miR-215-5p is a tumor suppressor in colorectal cancer (CRC); however, its role in metastasis remains unclear. This study evaluates the effects of miR-215 overexpression on the metastatic potential of CRC. Methods: CRC cell lines were stably transfected with [...] Read more.
Background: Growing evidence suggests that miR-215-5p is a tumor suppressor in colorectal cancer (CRC); however, its role in metastasis remains unclear. This study evaluates the effects of miR-215 overexpression on the metastatic potential of CRC. Methods: CRC cell lines were stably transfected with miR-215-5p and used for in vitro and in vivo functional analyses. Next-generation sequencing and RT-qPCR were performed to study changes on the mRNA level. Results: Overexpression of miR-215-5p significantly reduced the clonogenic potential, migration, and invasiveness of CRC cells in vitro and tumor weight and volume, and liver metastasis in vivo. Transcriptome analysis revealed mRNAs regulated by miR-215-5p and RT-qPCR confirmed results for seven selected genes. Significantly elevated levels of CTNNBIP1 were also observed in patients’ primary tumors and liver metastases compared to adjacent tissues, indicating its direct regulation by miR-215-5p. Gene Ontology and KEGG pathway analysis identified cellular processes and pathways associated with miR-215-5p deregulation. Conclusions: MiR-215-5p suppresses the metastatic potential of CRC cells through the regulation of divergent molecular pathways, including extracellular-matrix-receptor interaction and focal adhesion. Although the specific targets of miR-215-5p contributing to the formation of distant metastases must be further elucidated, this miRNA could serve as a promising target for CRC patients’ future therapeutic strategies. Full article
(This article belongs to the Special Issue microRNAs in Colorectal Cancer)
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Review

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35 pages, 5611 KiB  
Review
miRNA Clusters with Up-Regulated Expression in Colorectal Cancer
by Paulína Pidíková and Iveta Herichová
Cancers 2021, 13(12), 2979; https://doi.org/10.3390/cancers13122979 - 14 Jun 2021
Cited by 23 | Viewed by 2909
Abstract
Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally [...] Read more.
Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their members with respect to clinicopathological characteristics of patients. Based on available data, 15 up-regulated clusters, miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224, were selected. The positions of such clusters in the genome can be intronic or intergenic. Most clusters are regulated by several transcription factors, and miRNAs are also sponged by specific long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. Based on experimental evidence, 181 target genes of selected clusters were identified. Panther analysis was used to reveal the functions of the target genes and their corresponding pathways. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research. Full article
(This article belongs to the Special Issue microRNAs in Colorectal Cancer)
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17 pages, 342 KiB  
Review
The Clinical Assessment of MicroRNA Diagnostic, Prognostic, and Theranostic Value in Colorectal Cancer
by Hussein Al-Akhrass and Niki Christou
Cancers 2021, 13(12), 2916; https://doi.org/10.3390/cancers13122916 - 11 Jun 2021
Cited by 8 | Viewed by 2094
Abstract
MiRNAs have recently become a subject of great interest within cancers and especially colorectal cancers in diagnosis, prognosis, and therapy decisions; herein we review the current literature focusing on miRNAs in colorectal cancers, and we discuss future challenges to use this tool on [...] Read more.
MiRNAs have recently become a subject of great interest within cancers and especially colorectal cancers in diagnosis, prognosis, and therapy decisions; herein we review the current literature focusing on miRNAs in colorectal cancers, and we discuss future challenges to use this tool on a daily clinical basis. In liquid biopsies, miRNAs seem easily accessible and can give important information toward each step of the management of colorectal cancers. However, it is now necessary to highlight the most sensitive and specific miRNAs for each goal thanks to multicentric prospective studies. Conclusions: by their diversity and the feasibility of their use, miRNAs are getting part of the armamentarium of healthcare management of colorectal cancers. Full article
(This article belongs to the Special Issue microRNAs in Colorectal Cancer)
14 pages, 319 KiB  
Review
MicroRNAs in Rectal Cancer: Functional Significance and Promising Therapeutic Value
by Laura Imedio, Ion Cristóbal, Jaime Rubio, Andrea Santos, Federico Rojo and Jesús García-Foncillas
Cancers 2020, 12(8), 2040; https://doi.org/10.3390/cancers12082040 - 24 Jul 2020
Cited by 12 | Viewed by 1977
Abstract
It is well-known that microRNAs (miRNAs) are critical mediators of initiation and disease progression in many human cancers. Rectal cancer is a highly prevalent tumor, accounting for around one third of newly diagnosed colorectal cancers. The usefulness of miRNAs as clinical biomarkers predictive [...] Read more.
It is well-known that microRNAs (miRNAs) are critical mediators of initiation and disease progression in many human cancers. Rectal cancer is a highly prevalent tumor, accounting for around one third of newly diagnosed colorectal cancers. The usefulness of miRNAs as clinical biomarkers predictive of the outcome and response to chemoradiotherapy has been well-reported for rectal cancer. However, the existing literature on their functional and therapeutic impact needs to be put in context to clarify their role in disease pathogenesis. Therfore, this review is focused on the functional relevance of miRNAs as key regulators of signaling pathways in rectal cancer and their potential therapeutic value as novel molecular targets in this disease. Full article
(This article belongs to the Special Issue microRNAs in Colorectal Cancer)
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