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microRNA as a Biomarker in Gastroenterological Cancers
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microRNA as a Biomarker in Gastroenterological Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 24143

Special Issue Editors

Prof. Asahiro Morishita

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Guest Editor
Department of Gastroenterology and Neurology, Kagawa University, Takamatsu, Japan
Interests: liver disease; HCC; microRNA; biomarkers; metastasis; EMT
Prof. Dr. Tomoyuki Okumura

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Co-Guest Editor
Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama City, Japan
Interests: microRNA expression signature; esophageal squamous cell carcinoma
Dr. Yohei Shirakami

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Co-Guest Editor
Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
Interests: cancer prevention; gastroenterological disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gastroenterological cancer (GC) is one of the most leading cause of cancer death worldwide. In spite of improvements for GC therapy, the prognosis of those patients remains poor due to high incidence of recurrence. Better understanding of the pathogenesis during GC development brings effective outcomes for the diagnosis and treatment at early stages. MicroRNAs (miRNAs) are small endogenous non-coding single-stranded RNAs of 18-24 nucleotide-long molecules and modulate various target gene expressions at the post-transcriptional and translational levels. In various human malignancies, aberrant expression of miRNAs is a common and located in cancer associated genomic regions or fragile sites. As for the relationship between miRNAs and GC, several studies have demonstrated that the aberrant expression of specific miRNAs are detected in GC cells and tissues. However, little is known about the mechanisms of miRNA-related cell proliferation and development. Therefore, the finding of miRNAs has expanded our knowledge of the posttranscriptional gene regulation during GC development. Interestingly, more than half of all genes that encode miRNAs are located at fragile sites or in cancer-associated regions of the genome, suggesting the possibility of miRNAs as a diagnostic markers. In this Special Issue, we are looking for articles which deliver a profound insight of potential roles of miRNAs as useful diagnostic and prognostic markers in various GCs.

Prof. Asahiro Morishita
Guest Editor
Prof. Tomoyuki Okumura
Dr. Yohei Shirakami
Co-Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • Gastroenterological cancer
  • microRNA
  • epigenetic regulation
  • cancer development and metastasis
  • biomarkers

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Published Papers (7 papers)

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Editorial

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2 pages, 164 KiB  
Editorial
MicroRNA as a Biomarker in Gastroenterological Cancers
by Asahiro Morishita, Yohei Shirakami, Tomoyuki Okumura and Tsutomu Masaki
Int. J. Mol. Sci. 2022, 23(9), 4701; https://doi.org/10.3390/ijms23094701 - 24 Apr 2022
Viewed by 1615
Abstract
This Special Issue aims to highlight the usefulness of microRNA (miRNA) as diagnostic and prognostic markers of gastroenterological cancer (GC) [...] Full article
(This article belongs to the Special Issue microRNA as a Biomarker in Gastroenterological Cancers)

Research

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15 pages, 17538 KiB  
Article
Serum miR-373-3p and miR-194-5p Are Associated with Early Tumor Progression during FOLFIRINOX Treatment in Pancreatic Cancer Patients: A Prospective Multicenter Study
by Fleur van der Sijde, Marjolein Y. V. Homs, Marlies L. van Bekkum, Thierry P. P. van den Bosch, Koop Bosscha, Marc G. Besselink, Bert A. Bonsing, Jan Willem B. de Groot, Thomas M. Karsten, Bas Groot Koerkamp, Brigitte C. M. Haberkorn, Saskia A. C. Luelmo, Leonie J. M. Mekenkamp, Dana A. M. Mustafa, Johanna W. Wilmink, Casper H. J. van Eijck, Eveline E. Vietsch and on behalf of the Dutch Pancreatic Cancer Group
Int. J. Mol. Sci. 2021, 22(20), 10902; https://doi.org/10.3390/ijms222010902 - 9 Oct 2021
Cited by 12 | Viewed by 2698
Abstract
In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease [...] Read more.
In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort (n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD −0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10–14.49; miR-194-5p OR 0.91, 95% CI 0.83–0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX. Full article
(This article belongs to the Special Issue microRNA as a Biomarker in Gastroenterological Cancers)
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17 pages, 5258 KiB  
Article
RNA-Sequencing Based microRNA Expression Signature of Colorectal Cancer: The Impact of Oncogenic Targets Regulated by miR-490-3p
by Yuto Hozaka, Yoshiaki Kita, Ryutaro Yasudome, Takako Tanaka, Masumi Wada, Tetsuya Idichi, Kan Tanabe, Shunichi Asai, Shogo Moriya, Hiroko Toda, Shinichiro Mori, Hiroshi Kurahara, Takao Ohtsuka and Naohiko Seki
Int. J. Mol. Sci. 2021, 22(18), 9876; https://doi.org/10.3390/ijms22189876 - 13 Sep 2021
Cited by 7 | Viewed by 2609
Abstract
To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our [...] Read more.
To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease. Full article
(This article belongs to the Special Issue microRNA as a Biomarker in Gastroenterological Cancers)
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13 pages, 2083 KiB  
Article
Identification of Circulating Serum miRNAs as Novel Biomarkers in Pancreatic Cancer Using a Penalized Algorithm
by Jaehoon Lee, Hee Seung Lee, Soo Been Park, Chanyang Kim, Kahee Kim, Dawoon E. Jung and Si Young Song
Int. J. Mol. Sci. 2021, 22(3), 1007; https://doi.org/10.3390/ijms22031007 - 20 Jan 2021
Cited by 17 | Viewed by 2521
Abstract
Pancreatic cancer (PC) is difficult to detect in the early stages; thus, identifying specific and sensitive biomarkers for PC diagnosis is crucial, especially in the case of early-stage tumors. Circulating microRNAs are promising non-invasive biomarkers. Therefore, we aimed to identify non-invasive miRNA biomarkers [...] Read more.
Pancreatic cancer (PC) is difficult to detect in the early stages; thus, identifying specific and sensitive biomarkers for PC diagnosis is crucial, especially in the case of early-stage tumors. Circulating microRNAs are promising non-invasive biomarkers. Therefore, we aimed to identify non-invasive miRNA biomarkers and build a model for PC diagnosis. For the training model, blood serum samples from 63 PC patients and 63 control subjects were used. We selected 39 miRNA markers using a smoothly clipped absolute deviation-based penalized support vector machine and built a PC diagnosis model. From the double cross-validation, the average test AUC was 0.98. We validated the diagnosis model using independent samples from 25 PC patients and 81 patients with intrahepatic cholangiocarcinoma (ICC) and compared the results with those obtained from the diagnosis using carbohydrate antigen 19-9. For the markers miR-155-5p, miR-4284, miR-346, miR-7145-5p, miR-5100, miR-661, miR-22-3p, miR-4486, let-7b-5p, and miR-4703-5p, we conducted quantitative reverse transcription PCR using samples from 17 independent PC patients, 8 ICC patients, and 8 healthy individuals. Differential expression was observed in samples from PC patients. The diagnosis model based on the identified markers showed high sensitivity and specificity for PC detection and is potentially useful for early PC diagnosis. Full article
(This article belongs to the Special Issue microRNA as a Biomarker in Gastroenterological Cancers)
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Review

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17 pages, 1521 KiB  
Review
The Role of microRNAs in Cholangiocarcinoma
by Tingting Shi, Asahiro Morishita, Hideki Kobara and Tsutomu Masaki
Int. J. Mol. Sci. 2021, 22(14), 7627; https://doi.org/10.3390/ijms22147627 - 16 Jul 2021
Cited by 19 | Viewed by 3959
Abstract
Cholangiocarcinoma (CCA), an aggressive malignancy, is typically diagnosed at an advanced stage. It is associated with dismal 5-year postoperative survival rates, generating an urgent need for prognostic and diagnostic biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are associated with cancer [...] Read more.
Cholangiocarcinoma (CCA), an aggressive malignancy, is typically diagnosed at an advanced stage. It is associated with dismal 5-year postoperative survival rates, generating an urgent need for prognostic and diagnostic biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are associated with cancer regulation, including modulation of cell cycle progression, apoptosis, metastasis, angiogenesis, autophagy, therapy resistance, and epithelial–mesenchymal transition. Several miRNAs have been found to be dysregulated in CCA and are associated with CCA-related risk factors. Accumulating studies have indicated that the expression of altered miRNAs could act as oncogenic or suppressor miRNAs in the development and progression of CCA and contribute to clinical diagnosis and prognosis prediction as potential biomarkers. Furthermore, miRNAs and their target genes also contribute to targeted therapy development and aid in the determination of drug resistance mechanisms. This review aims to summarize the roles of miRNAs in the pathogenesis of CCA, their potential use as biomarkers of diagnosis and prognosis, and their utilization as novel therapeutic targets in CCA. Full article
(This article belongs to the Special Issue microRNA as a Biomarker in Gastroenterological Cancers)
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19 pages, 405 KiB  
Review
miRNAs Involved in Esophageal Carcinogenesis and miRNA-Related Therapeutic Perspectives in Esophageal Carcinoma
by Giovanni Zarrilli, Francesca Galuppini, Valentina Angerilli, Giada Munari, Marianna Sabbadin, Vanni Lazzarin, Lorenzo Nicolè, Rachele Biancotti and Matteo Fassan
Int. J. Mol. Sci. 2021, 22(7), 3640; https://doi.org/10.3390/ijms22073640 - 31 Mar 2021
Cited by 18 | Viewed by 2897
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that play a pivotal role in many aspects of cell biology, including cancer development. Within esophageal cancer, miRNAs have been proved to be involved in all phases of carcinogenesis, from initiation to metastatic spread. Several miRNAs have [...] Read more.
MicroRNAs (miRNAs) are small non-coding RNAs that play a pivotal role in many aspects of cell biology, including cancer development. Within esophageal cancer, miRNAs have been proved to be involved in all phases of carcinogenesis, from initiation to metastatic spread. Several miRNAs have been found to be dysregulated in esophageal premalignant lesions, namely Barrett’s esophagus, Barrett’s dysplasia, and squamous dysplasia. Furthermore, numerous studies have investigated the alteration in the expression levels of many oncomiRNAs and tumor suppressor miRNAs in esophageal squamous cell carcinoma and esophageal adenocarcinoma, thus proving how miRNAs are able modulate crucial regulatory pathways of cancer development. Considering these findings, miRNAs may have a role not only as a diagnostic and prognostic tool, but also as predictive biomarker of response to anti-cancer therapies and as potential therapeutic targets. This review aims to summarize several studies on the matter, focusing on the possible diagnostic–therapeutic implications. Full article
(This article belongs to the Special Issue microRNA as a Biomarker in Gastroenterological Cancers)
30 pages, 651 KiB  
Review
Molecular and Functional Roles of MicroRNAs in the Progression of Hepatocellular Carcinoma—A Review
by Kyoko Oura, Asahiro Morishita and Tsutomu Masaki
Int. J. Mol. Sci. 2020, 21(21), 8362; https://doi.org/10.3390/ijms21218362 - 7 Nov 2020
Cited by 89 | Viewed by 7140
Abstract
Liver cancer is the fourth leading cause of cancer deaths globally, of which hepatocellular carcinoma (HCC) is the major subtype. Viral hepatitis B and C infections, alcohol abuse, and metabolic disorders are multiple risk factors for liver cirrhosis and HCC development. Although great [...] Read more.
Liver cancer is the fourth leading cause of cancer deaths globally, of which hepatocellular carcinoma (HCC) is the major subtype. Viral hepatitis B and C infections, alcohol abuse, and metabolic disorders are multiple risk factors for liver cirrhosis and HCC development. Although great therapeutic advances have been made in recent decades, the prognosis for HCC patients remains poor due to late diagnosis, chemotherapy failure, and frequent recurrence. MicroRNAs (miRNAs) are endogenous, non-coding RNAs that regulate various molecular biological phenomena by suppressing the translation of target messenger RNAs (mRNAs). miRNAs, which often become dysregulated in malignancy, control cell proliferation, migration, invasion, and development in HCC by promoting or suppressing tumors. Exploring the detailed mechanisms underlying miRNA-mediated HCC development and progression can likely improve the outcomes of patients with HCC. This review summarizes the molecular and functional roles of miRNAs in the pathogenesis of HCC. Further, it elucidates the utility of miRNAs as novel biomarkers and therapeutic targets. Full article
(This article belongs to the Special Issue microRNA as a Biomarker in Gastroenterological Cancers)
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