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ncRNA
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Non-coding RNA as Biomarker in Cancer
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Non-coding RNA as Biomarker in Cancer

A special issue of Non-Coding RNA (ISSN 2311-553X). This special issue belongs to the section "Detection and Biomarkers of Non-Coding RNA".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 8906

Special Issue Editors

Dr. Luca Falzone

E-Mail Website
Guest Editor
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
Interests: molecular oncology; oncogenetics; epigenetics; biomarker discovery; drug resistance; microRNAs
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Daniela Calina

E-Mail Website
Guest Editor
Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Interests: clinical pharmacy; oncology; biomarkers; experimental pharmacology
Special Issues, Collections and Topics in MDPI journals
Dr. Giuseppe Gattuso

E-Mail Website
Guest Editor
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Interests: epigenetics; biomarker discovery; microRNAs; occupational carcinogens; molecular oncology; cancer; DNA methylation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer represents one of the main causes of death worldwide. Despite the advancement in diagnostic strategies and therapeutic interventions, this pathology is still responsible for millions of deaths annually, highlighting the need for novel diagnostic and prognostic biomarkers for a better management of tumors. In recent decades, several molecular mechanisms that are responsible for the development of tumors have been clarified; however, the precise pathogenetic role that is played by non-coding RNAs has not yet been elucidated. In this context, non-coding RNAs are emerging as novel promising biomarkers in oncology.

Non-coding RNAs, which were previously considered genomic “dark matter”, are now recognized for their intricate regulatory roles in the cellular processes underlying cancer development, as well as for their potential as promising biomarkers in cancer diagnostics and prognostics. Their dysregulation in various cancer types presents an opportunity for precise and early detection, offering insights into the disease progression and therapeutic responses.

On these bases, this Special Issue aims to delve into the significance of non-coding RNAs, such as microRNAs and long non-coding RNAs. Recent advancements and compelling evidence showcasing the utility of non-coding RNAs as accessible and specific biomarkers will be explored, paving the way for enhanced cancer diagnosis and personalized treatment strategies. This journey into the world of non-coding RNAs promises to unravel novel dimensions in the intricate landscape of cancer biomarker research.

Potential topics will include, but are not limited to the following:

  • The role of microRNAs in cancer;
  • The role of long non-coding RNAs in cancer;
  • Liquid biopsies and circulating non-coding RNAs;
  • Non-coding RNAs as diagnostic biomarkers;
  • Non-coding RNAs as prognostic biomarkers;
  • Non-coding RNAs as therapeutic targets in cancer;
  • Epigenetic alterations in cancer and their interplay with ncRNAs;
  • Emerging technologies in ncRNA research, such as next-generation sequencing and CRISPR-Cas systems.

Yours faithfully,

Dr. Luca Falzone
Prof. Dr. Daniela Calina
Dr. Giuseppe Gattuso
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. Non-Coding RNA 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 1800 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

  • cancer biomarkers
  • non-coding RNAs
  • cancer development
  • epigenetic alterations
  • microRNAs
  • long non-coding RNAs
  • liquid biopsies
  • personalized medicine
  • next-generation sequencing

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Published Papers (6 papers)

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Research

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20 pages, 2390 KiB  
Article
A miRNA Signature for Non-Invasive Colorectal Cancer Diagnosis in Morocco: miR-21, miR-29a and miR-92a
by Sofia Fathi, Oussama Aazzane, Salma Guendaoui, Nezha Tawfiq, Souha Sahraoui, Fadila Guessous and Mehdi Karkouri
Non-Coding RNA 2025, 11(2), 26; https://doi.org/10.3390/ncrna11020026 - 17 Mar 2025
Viewed by 511
Abstract
Colorectal cancer (CRC) is the third most diagnosed cancer and a leading cause of cancer-related mortality in Morocco, often detected at late stages. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for CRC detection, with miR-21, miR-29a, and miR-92a showing significant diagnostic [...] Read more.
Colorectal cancer (CRC) is the third most diagnosed cancer and a leading cause of cancer-related mortality in Morocco, often detected at late stages. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for CRC detection, with miR-21, miR-29a, and miR-92a showing significant diagnostic potential. This study aimed to evaluate the expression levels of these miRNAs in a Moroccan population and their efficacy as diagnostic biomarkers. Methods: A prospective study was conducted using blood samples from 50 CRC patients and 50 healthy controls. Circulating miRNA expression levels were quantified through reverse transcription quantitative PCR (RT-qPCR), with normalization to miR-1228-3p. Statistical analyses, including the Mann–Whitney U test, Receiver Operating Characteristic (ROC) curve analysis, sensitivity (Sen), and specificity (Spe) evaluations, were performed to assess the diagnostic accuracy of individual miRNAs and their combined performance as panels. Results: The expression levels of miR-21, miR-29a, and miR-92a were significantly elevated in CRC patients compared to healthy controls (all p < 0.001). ROC analysis demonstrated that miR-92a exhibited the highest individual diagnostic performance (AUC: 0.938), followed by miR-21 (AUC: 0.907) and miR-29a (AUC: 0.898). Sensitivity and specificity were 88% and 90%, 92% and 56%, and 76% and 94%, respectively. Combinatorial analysis revealed that the miR-29a and miR-92a panel achieved the highest diagnostic accuracy (AUC: 0.976), surpassing individual miRNAs and other combinations, highlighting its potential as a robust, non-invasive biomarker panel for CRC. Conclusions: This study highlights the potential of the miR-29a and miR-92a combination, which achieved excellent diagnostic efficiency (AUC: 0.976). These findings underscore miRNA utility in enhancing early detection and reducing CRC-related mortality in Morocco. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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11 pages, 1588 KiB  
Article
Circulating MicroRNAs in Patients with Vulvar Squamous Cell Carcinoma and Its Precursors
by Julia Rymuza, Angelika Długosz, Kamil Zalewski, Artur Kowalik, Mateusz Bujko and Magdalena Kowalewska
Non-Coding RNA 2025, 11(1), 13; https://doi.org/10.3390/ncrna11010013 - 7 Feb 2025
Viewed by 782
Abstract
Objectives: Vulvar squamous cell carcinoma (VSCC) is a rare gynecologic malignancy, with most cases arising from differentiated vulvar intraepithelial neoplasia (dVIN). Approximately one-third of VSCC cases originate from high-grade squamous intraepithelial lesions (HSILs), which are associated with persistent infection by varieties of [...] Read more.
Objectives: Vulvar squamous cell carcinoma (VSCC) is a rare gynecologic malignancy, with most cases arising from differentiated vulvar intraepithelial neoplasia (dVIN). Approximately one-third of VSCC cases originate from high-grade squamous intraepithelial lesions (HSILs), which are associated with persistent infection by varieties of high-risk human papillomavirus (hrHPV). This study aimed to quantify the circulating microRNAs (miRNAs) in the plasma of patients with premalignant conditions (dVIN and HSILs) and VSCC using TaqMan Low-Density Arrays. Methods: Plasma samples were collected from 40 patients, including those treated for HSILs, dVIN, and VSCC. Quantitative real-time PCR (qRT-PCR) identified the circulating miRNAs differentially expressed in the plasma of VSCC patients compared to patients with precancerous lesions. Results: A total of 31 differentially expressed miRNAs (DEMs) were found to be significantly upregulated in plasma from VSCC patients compared to precancerous cases. None of the analyzed miRNAs were able to distinguish VSCC cases based on hrHPV tumor status. Conclusions: This study provides strong evidence that a distinct set of miRNAs can differentiate between plasma samples from VSCC patients and those with precancerous lesions. Thus, these DEMs have potential diagnostic and prognostic value. “Predisposing” DEMs could be developed as biomarkers to aid in the assessment of vulvar lesions, helping to exclude or confirm progression toward cancer. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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15 pages, 4653 KiB  
Article
Identification of Tumor-Suppressive miR-30a-3p Controlled Genes: ANLN as a Therapeutic Target in Breast Cancer
by Reiko Mitsueda, Ayako Nagata, Hiroko Toda, Yuya Tomioka, Ryutaro Yasudome, Mayuko Kato, Yoshiaki Shinden, Akihiro Nakajo and Naohiko Seki
Non-Coding RNA 2024, 10(6), 60; https://doi.org/10.3390/ncrna10060060 - 30 Nov 2024
Viewed by 1221
Abstract
Our recently created RNA-sequence-based microRNA (miRNA) expression signature in breast cancer clinical specimens revealed that some miR-30 family members were significantly downregulated in cancer tissues. Based on TCGA database analyses, we observed that among the miR-30 family members, miR-30a-3p (the passenger strand derived [...] Read more.
Our recently created RNA-sequence-based microRNA (miRNA) expression signature in breast cancer clinical specimens revealed that some miR-30 family members were significantly downregulated in cancer tissues. Based on TCGA database analyses, we observed that among the miR-30 family members, miR-30a-3p (the passenger strand derived from pre-miR-30a) was significantly downregulated in breast cancer (BC) clinical specimens, and its low expression predicted worse prognoses. Ectopic expression assays showed that miR-30a-3p transfected cancer cells (MDA-MB-157 and MDA-MB-231) had their aggressive phenotypes significantly suppressed, e.g., their proliferation, migration, and invasion abilities. These data indicated that miR-30a-3p acted as a tumor-suppressive miRNA in BC cells. Our subsequent search for miR-30a-3p controlled molecular networks in BC cells yielded a total of 189 genes. Notably, among those 189 genes, cell-cycle-related genes (ANLN, MKI67, CCNB1, NCAPG, ZWINT, E2F7, PDS5A, RIF1, BIRC5, MAD2L1, CACUL1, KIF23, UBE2S, EML4, SEPT10, CLTC, and PCNP) were enriched according to a GeneCodis 4 database analysis. Moreover, the overexpression of four genes (ANLN, CCNB1, BIRC5, and KIF23) significantly predicted worse prognoses for patients with BC according to TCGA analyses. Finally, our assays demonstrated that the overexpression of ANLN had cancer-promoting functions in BC cells. The involvement of miR-30a-3p (the passenger strand) in BC molecular pathogenesis is a new concept in cancer research, and the outcomes of our study strongly indicate the importance of analyzing passenger strands of miRNAs in BC cells. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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21 pages, 1627 KiB  
Article
High Sensitivity and Specificity Platform to Validate MicroRNA Biomarkers in Cancer and Human Diseases
by Anastassia Kanavarioti, M. Hassaan Rehman, Salma Qureshi, Aleena Rafiq and Madiha Sultan
Non-Coding RNA 2024, 10(4), 42; https://doi.org/10.3390/ncrna10040042 - 22 Jul 2024
Cited by 2 | Viewed by 2669
Abstract
We developed a technology for detecting and quantifying trace nucleic acids using a bracketing protocol designed to yield a copy number with approximately ± 20% accuracy across all concentrations. The microRNAs (miRNAs) let-7b, miR-15b, miR-21, miR-375 and miR-141 were measured in serum and [...] Read more.
We developed a technology for detecting and quantifying trace nucleic acids using a bracketing protocol designed to yield a copy number with approximately ± 20% accuracy across all concentrations. The microRNAs (miRNAs) let-7b, miR-15b, miR-21, miR-375 and miR-141 were measured in serum and urine samples from healthy subjects and patients with breast, prostate or pancreatic cancer. Detection and quantification were amplification-free and enabled using osmium-tagged probes and MinION, a nanopore array detection device. Combined serum from healthy men (Sigma-Aldrich, St. Louis, MO, USA #H6914) was used as a reference. Total RNA isolated from biospecimens using commercial kits was used as the miRNA source. The unprecedented ± 20% accuracy led to the conclusion that miRNA copy numbers must be normalized to the same RNA content, which in turn illustrates (i) independence from age, sex and ethnicity, as well as (ii) equivalence between serum and urine. miR-21, miR-375 and miR-141 copies in cancers were 1.8-fold overexpressed, exhibited zero overlap with healthy samples and had a p-value of 1.6 × 10−22, tentatively validating each miRNA as a multi-cancer biomarker. miR-15b was confirmed to be cancer-independent, whereas let-7b appeared to be a cancer biomarker for prostate and breast cancer, but not for pancreatic cancer. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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Review

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25 pages, 1618 KiB  
Review
Non-Coding RNA as a Biomarker in Lung Cancer
by Chahat Suri, Shashikant Swarnkar, LVKS Bhaskar and Henu Kumar Verma
Non-Coding RNA 2024, 10(5), 50; https://doi.org/10.3390/ncrna10050050 - 30 Sep 2024
Cited by 4 | Viewed by 2579
Abstract
Introduction: Lung cancer remains one of the most prevalent and deadly cancers globally, with high mortality rates largely due to late-stage diagnosis, aggressive progression, and frequent recurrence. Despite advancements in diagnostic techniques and therapeutic interventions, the overall prognosis for lung cancer patients continues [...] Read more.
Introduction: Lung cancer remains one of the most prevalent and deadly cancers globally, with high mortality rates largely due to late-stage diagnosis, aggressive progression, and frequent recurrence. Despite advancements in diagnostic techniques and therapeutic interventions, the overall prognosis for lung cancer patients continues to be dismal. Method: Emerging research has identified non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, as critical regulators of gene expression, significantly influencing cancer biology. These ncRNAs play pivotal roles in various aspects of lung cancer pathogenesis, including tumor initiation, progression, metastasis, and resistance to therapy. Results: We provide a comprehensive analysis of the current understanding of ncRNAs in lung cancer, emphasizing their potential as biomarkers for early diagnosis, prognostication, and the prediction of the therapeutic response. We explore the biological functions of ncRNAs, their involvement in key oncogenic pathways, and the molecular mechanisms by which they modulate gene expression and cellular processes in lung cancer. Furthermore, this review highlights recent advances in ncRNA-based diagnostic tools and therapeutic strategies, such as miRNA mimics and inhibitors, lncRNA-targeted therapies, and circRNA-modulating approaches, offering promising avenues for personalized medicine. Conclusion: Finally, we discuss the challenges and future directions in ncRNA research, including the need for large-scale validation studies and the development of efficient delivery systems for ncRNA-based therapies. This review underscores the potential of ncRNAs to revolutionize lung cancer management by providing novel diagnostic and therapeutic options that could improve patient outcomes. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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Other

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30 pages, 2375 KiB  
Systematic Review
Building a Hand-Curated ceRNET for Endometrial Cancer, Striving for Clinical as Well as Medicolegal Soundness: A Systematic Review
by Roberto Piergentili, Stefano Sechi, Lina De Paola, Simona Zaami and Enrico Marinelli
Non-Coding RNA 2025, 11(3), 34; https://doi.org/10.3390/ncrna11030034 - 30 Apr 2025
Viewed by 89
Abstract
Background/Objectives: Competing endogenous RNAs (ceRNA) are molecules that compete for the binding to a microRNA (miR). Usually, there are two ceRNA, one of which is a protein-coding RNA (mRNA), with the other being a long non-coding RNA (lncRNA). The miR role is to [...] Read more.
Background/Objectives: Competing endogenous RNAs (ceRNA) are molecules that compete for the binding to a microRNA (miR). Usually, there are two ceRNA, one of which is a protein-coding RNA (mRNA), with the other being a long non-coding RNA (lncRNA). The miR role is to inhibit mRNA expression, either promoting its degradation or impairing its translation. The lncRNA can “sponge” the miR, thus impeding its inhibitory action on the mRNA. In their easier configuration, these three molecules constitute a regulatory axis for protein expression. However, each RNA can interact with multiple targets, creating branched and intersected axes that, all together, constitute what is known as a competing endogenous RNA network (ceRNET). Methods: In this systematic review, we collected all available data from PubMed about experimentally verified (by luciferase assay) regulatory axes in endometrial cancer (EC), excluding works not using this test; Results: This search allowed the selection of 172 bibliographic sources, and manually building a series of ceRNETs of variable complexity showed the known axes and the deduced intersections. The main limitation of this search is the highly stringent selection criteria, possibly leading to an underestimation of the complexity of the networks identified. However, this work allows us not only to hypothesize possible gap fillings but also to set the basis to instruct artificial intelligence, using adequate prompts, to expand the EC ceRNET by comparing it with ceRNETs of other cancers. Moreover, these networks can be used to inform and guide research toward specific, though still unidentified, axes in EC, to complete parts of the network that are only partially described, or even to integrate low complexity subnetworks into larger more complex ones. Filling the gaps among the existing EC ceRNET will allow physicians to hypothesize new therapeutic strategies that may either potentiate or substitute existing ones. Conclusions: These ceRNETs allow us to easily visualize long-distance interactions, thus helping to select the best treatment, depending on the molecular profile of each patient, for personalized medicine. This would yield higher efficiency rates and lower toxicity levels, both of which are extremely relevant factors not only for patients’ wellbeing, but also for the legal, regulatory, and ethical aspects of miR-based innovative treatments and personalized medicine as a whole. This systematic review has been registered in PROSPERO (ID: PROSPERO 2025 CRD420251035222). Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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