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Hallmark Properties and Behind-the-Scenes Role of Non-coding RNAs in Gastrointestinal...
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Hallmark Properties and Behind-the-Scenes Role of Non-coding RNAs in Gastrointestinal Cancers’ Onset, Progression and Metastasis

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

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 6741

Special Issue Editors

Dr. Gabriella Misso

E-Mail Website
Guest Editor
Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
Interests: cancer; cell death pathways; miRNA; long non-coding RNA; cell signaling; apoptosis; autophagy; nanotechnology; drug delivery; chemotherapy; combination therapy; target-therapy; immunotherapy; biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Alessia Maria Cossu

E-Mail Website
Guest Editor
Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, Italy
Interests: prostate cancer; laryngeal cancer; colorectal cancer
Dr. Michela Falco

E-Mail Website
Guest Editor
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Interests: laryngeal cancer; prostate cancer

Special Issue Information

Dear Colleagues,

Gastrointestinal (GI) cancers encompass a heterogeneous group of neoplastic diseases sharing some common risk factors but differing in etiology, prognosis and clinical management across the various tumor types. The main malignant conditions of the GI tract involve, in order, colorectum, stomach, liver, esophagus and pancreas.

Understanding the molecular basis of GI cancers is a crucial point for the development of new diagnostic and therapeutic strategies. Extensive genomic studies revealed recurrent mutations or copy number variations frequently located in non-coding DNA regions, suggesting their impact on the emerging complexities underlying the development and progression of GI neoplasms. Non-coding genomic regions cover 95% of the whole DNA and are, for the most part, transcribed into functional non-coding RNAs (ncRNAs), including microRNAs (miRNAs), endogenous small interfering RNAs (endo-siRNAs), small nucleolar RNAs (snoRNAs), circular RNA (circRNA), and long non-coding RNAs (lncRNAs), which represent the largest class of non-coding transcripts. ncRNAs are dysregulated in various tumor processes, including GI cancer initiation, metastasis, and resistance to therapy. They can create a complex network of mutual interactions acting as either oncogenes or tumor suppressors in a tissue-specific manner. In this frame, ncRNAs are considered promising diagnostic, prognostic and therapeutic targets.

This Special Issue will report the most recent advances in understanding ncRNAs’ role in GI neoplasms’ tumorigenesis and progression, focusing on their application as tumor markers and therapeutic agents.

Dr. Gabriella Misso
Dr. Alessia Maria Cossu
Dr. Michela Falco
Guest Editors

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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gastrointestinal cancers
  • miRNA
  • lncRNA
  • oncogene
  • tumor suppressor
  • colon cancer
  • gastric cancer
  • hepatocellular carcinoma
  • pancreatic cancer

Published Papers (5 papers)

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Research

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21 pages, 3530 KiB  
Article
Identification of Tissue miRNA Signatures for Pancreatic Ductal Adenocarcinoma
by Carlo Caputo, Michela Falco, Anna Grimaldi, Angela Lombardi, Chiara Carmen Miceli, Mariateresa Cocule, Marco Montella, Luca Pompella, Giuseppe Tirino, Severo Campione, Chiara Tammaro, Antonio Cossu, Grazia Fenu Pintori, Margherita Maioli, Donatella Coradduzza, Giovanni Savarese, Antonio Fico, Alessandro Ottaiano, Giovanni Conzo, Madhura S. Tathode, Fortunato Ciardiello, Michele Caraglia, Ferdinando De Vita and Gabriella Missoadd Show full author list remove Hide full author list
Cancers 2024, 16(4), 824; https://doi.org/10.3390/cancers16040824 - 18 Feb 2024
Cited by 1 | Viewed by 979
Abstract
Pancreatic ductal adenocarcinoma (PDAC), a neoplasm of the gastrointestinal tract, is the most common pancreatic malignancy (90%) and the fourth highest cause of cancer mortality worldwide. Surgery intervention is currently the only strategy able to offer an advantage in terms of overall survival, [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC), a neoplasm of the gastrointestinal tract, is the most common pancreatic malignancy (90%) and the fourth highest cause of cancer mortality worldwide. Surgery intervention is currently the only strategy able to offer an advantage in terms of overall survival, but prognosis remains poor even for operated patients. Therefore, the development of robust biomarkers for early diagnosis and prognostic stratification in clinical practice is urgently needed. In this work, we investigated deregulated microRNAs (miRNAs) in tissues from PDAC patients with high (G3) or low (G2) histological grade and with (N+) or without (N−) lymph node metastases. miRNA expression profiling was performed by a comprehensive PCR array and subsequent validation by RT-qPCR. The results showed a significant increase in miR-1-3p, miR-31-5p, and miR-205-5p expression in G3 compared to G2 patients (** p < 0.01; *** p < 0.001; *** p < 0.001). miR-518d-3p upregulation and miR-215-5p downregulation were observed in N+ compared to N− patients. A statistical analysis performed using OncomiR program showed the significant involvement (p < 0.05) of two miRNAs (miR-31 and miR-205) in the histological grade of PDAC patients. Also, an expression analysis in PDAC patients showed that miR-31 and miR-205 had the highest expression at grade 3 compared with normal and other tumor grades. Overall, survival plots confirmed that the overexpression of miR-31 and miR-205 was significantly correlated with decreased survival in TCGA PDAC clinical samples. A KEGG pathway analysis showed that all three miRNAs are involved in the regulation of multiple pathways, including the Hippo signaling, adherens junction and microRNAs in cancer, along with several target genes. Based on in silico analysis and experimental validation, our study suggests the potential role of miR-1-3p, miR-31-5p, and miR-205-5p as useful clinical biomarkers and putative therapeutic targets in PDAC, which should be further investigated to determine the specific molecular processes affected by their aberrant expression. Full article
(This article belongs to the Special Issue Hallmark Properties and Behind-the-Scenes Role of Non-coding RNAs in Gastrointestinal Cancers’ Onset, Progression and Metastasis)
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Review

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29 pages, 5606 KiB  
Review
Noncoding RNAs in Hepatocellular Carcinoma: Potential Applications in Combined Therapeutic Strategies and Promising Candidates of Treatment Response
by Clara Vianello, Elisa Monti, Ilaria Leoni, Giuseppe Galvani, Catia Giovannini, Fabio Piscaglia, Claudio Stefanelli, Laura Gramantieri and Francesca Fornari
Cancers 2024, 16(4), 766; https://doi.org/10.3390/cancers16040766 - 13 Feb 2024
Viewed by 889
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing, and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinically available treatments has dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have [...] Read more.
The incidence of hepatocellular carcinoma (HCC) is increasing, and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinically available treatments has dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have improved the overall survival of patients, showing a durable treatment benefit over time and a different response pattern with respect to tyrosine kinase inhibitors (TKIs). Although there is improved survival in responder cases, a sizeable group of patients are primary progressors or are ineligible for immunotherapy. Indeed, patients with nonviral etiologies, such as nonalcoholic steatohepatitis (NASH), and alterations in specific driver genes might be less responsive to immunotherapy. Therefore, improving the comprehension of mechanisms of drug resistance and identifying biomarkers that are informative of the best treatment approach are required actions to improve patient survival. Abundant evidence indicates that noncoding RNAs (ncRNAs) are pivotal players in cancer. Molecular mechanisms through which ncRNAs exert their effects in cancer progression and drug resistance have been widely investigated. Nevertheless, there are no studies summarizing the synergistic effect between ncRNA-based strategies and TKIs or ICIs in the preclinical setting. This review aims to provide up-to-date information regarding the possible use of ncRNAs as therapeutic targets in association with molecular-targeted agents and immunotherapies and as predictive tools for the selection of optimized treatment options in advanced HCCs. Full article
(This article belongs to the Special Issue Hallmark Properties and Behind-the-Scenes Role of Non-coding RNAs in Gastrointestinal Cancers’ Onset, Progression and Metastasis)
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35 pages, 3714 KiB  
Review
Role of Non-Coding RNAs in Hepatocellular Carcinoma Progression: From Classic to Novel Clinicopathogenetic Implications
by Mario Romeo, Marcello Dallio, Flavia Scognamiglio, Lorenzo Ventriglia, Marina Cipullo, Annachiara Coppola, Chiara Tammaro, Giuseppe Scafuro, Patrizia Iodice and Alessandro Federico
Cancers 2023, 15(21), 5178; https://doi.org/10.3390/cancers15215178 - 27 Oct 2023
Cited by 1 | Viewed by 1545
Abstract
Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a [...] Read more.
Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as “small ncRNAs” (sncRNAs) and “long ncRNAs” (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. In this review, we describe the main dysregulated ncRNAs and the relative molecular pathways involved in HCC progression, analyzing their implications in certain etiologically related contexts, and their applicability in clinical practice as novel diagnostic, prognostic, and therapeutic tools. Finally, given the growing evidence supporting the immune system response, the oxidative stress-regulated mechanisms, and the gut microbiota composition as relevant emerging elements mutually influencing liver-cancerogenesis processes, we investigate the relationship of ncRNAs with this triad, shedding light on novel pathogenetic frontiers of HCC progression. Full article
(This article belongs to the Special Issue Hallmark Properties and Behind-the-Scenes Role of Non-coding RNAs in Gastrointestinal Cancers’ Onset, Progression and Metastasis)
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26 pages, 1459 KiB  
Review
Clinical Significance of Non-Coding RNA Regulation of Programmed Cell Death in Hepatocellular Carcinoma
by Wuyu Chen, Minghao Ruan, Minghao Zou, Fuchen Liu and Hui Liu
Cancers 2023, 15(16), 4187; https://doi.org/10.3390/cancers15164187 - 21 Aug 2023
Cited by 1 | Viewed by 1055
Abstract
Hepatocellular carcinoma (HCC) is a widely prevalent and malignantly progressive tumor. Most patients are typically diagnosed with HCC at an advanced stage, posing significant challenges in the execution of curative surgical interventions. Non-coding RNAs (ncRNAs) represent a distinct category of RNA molecules not [...] Read more.
Hepatocellular carcinoma (HCC) is a widely prevalent and malignantly progressive tumor. Most patients are typically diagnosed with HCC at an advanced stage, posing significant challenges in the execution of curative surgical interventions. Non-coding RNAs (ncRNAs) represent a distinct category of RNA molecules not directly involved in protein synthesis. However, they possess the remarkable ability to regulate gene expression, thereby exerting significant regulatory control over cellular processes. Notably, ncRNAs have been implicated in the modulation of programmed cell death (PCD), a crucial mechanism that various therapeutic agents target in the fight against HCC. This review summarizes the clinical significance of ncRNA regulation of PCD in HCC, including patient diagnosis, prognosis, drug resistance, and side effects. The aim of this study is to provide new insights and directions for the diagnosis and drug treatment strategies of HCC. Full article
(This article belongs to the Special Issue Hallmark Properties and Behind-the-Scenes Role of Non-coding RNAs in Gastrointestinal Cancers’ Onset, Progression and Metastasis)
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27 pages, 2243 KiB  
Review
Lynch Syndrome Biopathology and Treatment: The Potential Role of microRNAs in Clinical Practice
by Serena Ascrizzi, Grazia Maria Arillotta, Katia Grillone, Giulio Caridà, Stefania Signorelli, Asad Ali, Caterina Romeo, Pierfrancesco Tassone and Pierosandro Tagliaferri
Cancers 2023, 15(15), 3930; https://doi.org/10.3390/cancers15153930 - 02 Aug 2023
Viewed by 1338
Abstract
Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2–3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the [...] Read more.
Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2–3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). Despite the fact that the genetics of the vast majority of MSI-positive (MSI+) cancers can be explained, the etiology of this specific subset is still poorly understood. As a possible new mechanism, it has been recently demonstrated that the overexpression of certain microRNAs (miRNAs, miRs), such as miR-155, miR-21, miR-137, can induce MSI or modulate the expression of the genes involved in LS pathogenesis. MiRNAs are small RNA molecules that regulate gene expression at the post-transcriptional level by playing a critical role in the modulation of key oncogenic pathways. Increasing evidence of the link between MSI and miRNAs in LS prompted a deeper investigation into the miRNome involved in these diseases. In this regard, in this study, we discuss the emerging role of miRNAs as crucial players in the onset and progression of LS as well as their potential use as disease biomarkers and therapeutic targets in the current view of precision medicine. Full article
(This article belongs to the Special Issue Hallmark Properties and Behind-the-Scenes Role of Non-coding RNAs in Gastrointestinal Cancers’ Onset, Progression and Metastasis)
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