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Non-coding RNA (ncRNA) in Cancer
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Non-coding RNA (ncRNA) in Cancer

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

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 25802

Special Issue Editors

Prof. Dr. Damjan Glavač

E-Mail Website
Guest Editor
Department of Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
Interests: molecular medicine; novel diagnostic approaches; genetic diseases; cancer; next generation sequencing; mutation detection; non-coding RNAs as biomarkers
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Metka Ravnik-Glavač

E-Mail Website
Co-Guest Editor
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
Interests: regulation of gene expretion through epigenetics and non-coding RNAs; genetic polymorphysms and mutations; non coding RNAs (miRNAs, lncRNAs, circRNAs) as circulating biomarkers in diseases of neurodegeneration and cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the last three decades, researchers have discovered multiple types of RNA, including non-coding RNAs (ncRNAs) that are in general not involved in the production of proteins. ncRNAs include small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), guide RNAs (gRNAs), RNaseP RNAs, transfer RNAs (tRNAs), ribosome RNAs (rRNAs), transfer messenger RNAs (tmRNAs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), piwi interaction RNAs (piRNAs), circular RNAs (circRNAs), and Y RNA (YRNA).

ncRNAs constitute almost 60% of the transcriptome of human cells, and are involved in the regulation of cellular processes and pathways in health and disease. The field of non-coding RNA research in cancer started in 2002, only two years after the discovery of the first human miRNA (let-7). In patients with B-cell chronic lymphocytic leukemia, two miRNA genes, mir-15a and mir-16-1, were identified within chromosomal region 13q14. Both miRNAs were either deleted or downregulated, suggesting their potential role as tumor suppressors. Since then, the ncRNA research field has grown exponentially. More recently, two classes of ncRNAs, long non-coding RNA (lncRNA), defined by RNA transcripts longer than 200 nucleotides, and circular RNA (circRNA), defined as endogenous ncRNA that has a non-polyadenylated, closed, single-stranded, and continuous loop structure, have been shown to have a functional role in cancer.

Novel RNA sequencing technologies and bioinformatics approaches have revealed not only novel types of ncRNAs but also elucidated the role of many ncRNAs in carcinogenesis. Usually, different ncRNAs interact with each other and form a highly complex regulatory network that controls important cellular programs. Disturbances to these programs lead to widespread changes in the fate of cells and contribute to development of cancer. A vast amount of data on ncRNAs has been generated, collected, and organized using computational approaches.

In this Special Issue, we will cover recent advances in any of the roles of ncRNA in cancer, such as function, mechanism of action, mode of interaction, as well as clinical studies. We welcome contributions in the form of original research articles and reviews.

Prof. Damjan Glavač
Guest Editor
Prof. Metka Ravnik-Glavač
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.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • non-coding RNA (ncRNA)
  • cancer
  • oncogenes
  • tumor suppressor genes
  • microRNA
  • lncRNA
  • circRNA
  • cancer biomarkers

Published Papers (7 papers)

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Research

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12 pages, 2468 KiB  
Article
Long Non-Coding RNA MIR31HG Promotes the Transforming Growth Factor β-Induced Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma Cells
by Ching-Chung Ko, Yao-Yu Hsieh and Pei-Ming Yang
Int. J. Mol. Sci. 2022, 23(12), 6559; https://doi.org/10.3390/ijms23126559 - 12 Jun 2022
Cited by 5 | Viewed by 1722
Abstract
The epithelial-to-mesenchymal transition (EMT) describes a biological process in which polarized epithelial cells are converted into highly motile mesenchymal cells. It promotes cancer cell dissemination, allowing them to form distal metastases, and also involves drug resistance in metastatic cancers. Transforming growth factor β [...] Read more.
The epithelial-to-mesenchymal transition (EMT) describes a biological process in which polarized epithelial cells are converted into highly motile mesenchymal cells. It promotes cancer cell dissemination, allowing them to form distal metastases, and also involves drug resistance in metastatic cancers. Transforming growth factor β (TGFβ) is a multifunctional cytokine that plays essential roles in development and carcinogenesis. It is a major inducer of the EMT. The MIR31 host gene (MIR31HG) is a newly identified long non-coding (lnc)RNA that exhibits ambiguous roles in cancer. In this study, a cancer genomics analysis predicted that MIR31HG overexpression was positively correlated with poorer disease-free survival of pancreatic ductal adenocarcinoma (PDAC) patients, which was associated with upregulation of genes related to TGFβ signaling and the EMT. In vitro evidence demonstrated that TGFβ induced MIR31HG expression in PDAC cells, and knockdown of MIR31HG expression reversed TGFβ-induced EMT phenotypes and cancer cell migration. Therefore, MIR31HG has an oncogenic role in PDAC by promoting the EMT. Full article
(This article belongs to the Special Issue Non-coding RNA (ncRNA) in Cancer)
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17 pages, 2896 KiB  
Article
Synthetic Circular miR-21 Sponge as Tool for Lung Cancer Treatment
by Ana R. Rama, Francisco Quiñonero, Cristina Mesas, Consolación Melguizo and Jose Prados
Int. J. Mol. Sci. 2022, 23(6), 2963; https://doi.org/10.3390/ijms23062963 - 09 Mar 2022
Cited by 10 | Viewed by 2431
Abstract
Lung cancer is the most common cancer in the world and several miRNAs are associated with it. MiRNA sponges are presented as tools to inhibit miRNAs. We designed a system to capture miRNAs based on circular RNAs (circRNA). To demonstrate its usefulness, we [...] Read more.
Lung cancer is the most common cancer in the world and several miRNAs are associated with it. MiRNA sponges are presented as tools to inhibit miRNAs. We designed a system to capture miRNAs based on circular RNAs (circRNA). To demonstrate its usefulness, we chose miR-21, which is upregulated and implicated in lung cancer. We constructed a miR-21 sponge and inserted it into a vector that facilitates circular RNA production (Circ-21) to study its effect on growth, colony formation, and migration in lung cancer cell lines and multicellular tumor spheroids (MTS). Circ-21 induced a significant and time-dependent decrease in the growth of A549 and LL2 cells, but not in L132 cells. Furthermore, A549 and LL2 cells transfected with Circ-21 showed a lower number of colonies and migration than L132. Similar findings were seen in A549 and LL2 Circ-21 MTS, which showed a significant decrease in volume growth, but not in L132 Circ-21 MTS. Based on this, the miR-21 circular sponge may suppress the processes of tumorigenesis and progression. Therefore, our system based on circular sponges seems to be effective, as a tool for the capture of other miRNAs. Full article
(This article belongs to the Special Issue Non-coding RNA (ncRNA) in Cancer)
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18 pages, 2373 KiB  
Article
New Circulating Circular RNAs with Diagnostic and Prognostic Potential in Advanced Colorectal Cancer
by Maria Radanova, Galya Mihaylova, Oskan Tasinov, Desislava P. Ivanova, George St. Stoyanov, Neshe Nazifova-Tasinova, Rostislav Manev, Ayshe Salim, Miglena Nikolova, Diana G. Ivanova, Nikolay Conev, Zhasmina Mihaylova and Ivan Donev
Int. J. Mol. Sci. 2021, 22(24), 13283; https://doi.org/10.3390/ijms222413283 - 10 Dec 2021
Cited by 10 | Viewed by 2433
Abstract
Circular RNAs (circRNAs) are a group of special endogenous long non-coding RNAs which are highly stable in the circulation, and, thus, more suitable as new biomarkers of colorectal cancer (CRC). The aim of our study was to explore the plasma expression levels of [...] Read more.
Circular RNAs (circRNAs) are a group of special endogenous long non-coding RNAs which are highly stable in the circulation, and, thus, more suitable as new biomarkers of colorectal cancer (CRC). The aim of our study was to explore the plasma expression levels of four circRNAs: has_circ_0001445, hsa_circ_0003028, hsa_circ_0007915 and hsa_circ_0008717 in patients with CRC and to evaluate their associations with clinicopathological characteristics and the clinical outcome of the patients. CircRNAs were extracted from patients’ plasma obtained prior to chemotherapy. Their expression levels were measured by qPCR and calculated applying the 2−ΔΔCt method. The levels of all four circRNAs were significantly increased in the plasma of CRC patients. At the optimal cut-off values hsa_circ_0001445 and hsa_circ_0007915 in plasma could significantly distinguish between patients with or without metastatic CRC with 92.56% sensitivity and 42.86% specificity, and with 86.07% sensitivity and 57.14% specificity, respectively. The mean overall survival (OS) of patients with high/intermediate expression of hsa_circ_0001445 was 30 months, significantly higher in comparison with the mean OS of the patients with low expression—20 months (log-rank test, p = 0.034). In multivariate Cox regression analysis, the low levels of hsa_circ_0001445 were also associated with shorter survival (HR = 1.59, 95% CI: 1.02–2.47, p = 0.040). A prognostic significance of hsa_circ_0001445 for patients with metastatic CRC was established. Full article
(This article belongs to the Special Issue Non-coding RNA (ncRNA) in Cancer)
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Review

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15 pages, 315 KiB  
Review
The Role of MicroRNA as Clinical Biomarkers for Breast Cancer Surgery and Treatment
by Matthew G. Davey, Molly Davies, Aoife J. Lowery, Nicola Miller and Michael J. Kerin
Int. J. Mol. Sci. 2021, 22(15), 8290; https://doi.org/10.3390/ijms22158290 - 01 Aug 2021
Cited by 27 | Viewed by 3773
Abstract
Breast cancer is the most common cancer diagnosed in women. In recent times, survival outcomes have improved dramatically in accordance with our enhanced understanding of the molecular processes driving breast cancer proliferation and development. Refined surgical approaches, combined with novel and targeted treatment [...] Read more.
Breast cancer is the most common cancer diagnosed in women. In recent times, survival outcomes have improved dramatically in accordance with our enhanced understanding of the molecular processes driving breast cancer proliferation and development. Refined surgical approaches, combined with novel and targeted treatment options, have aided the personalisation of breast cancer patient care. Despite this, some patients will unfortunately succumb to the disease. In recent times, translational research efforts have been focused on identifying novel biomarkers capable of informing patient outcome; microRNAs (miRNAs) are small non-coding molecules, which regulate gene expression at a post-transcriptional level. Aberrant miRNA expression profiles have been observed in cancer proliferation and development. The measurement and correlation of miRNA expression levels with oncological outcomes such as response to current conventional therapies, and disease recurrence are being investigated. Herein, we outline the clinical utility of miRNA expression profiles in informing breast cancer prognosis, predicting response to treatment strategies as well as their potential as therapeutic targets to enhance treatment modalities in the era of precision oncology. Full article
(This article belongs to the Special Issue Non-coding RNA (ncRNA) in Cancer)
17 pages, 6869 KiB  
Review
Long Noncoding RNA GAS5 in Breast Cancer: Epigenetic Mechanisms and Biological Functions
by Elena A. Filippova, Marina V. Fridman, Alexey M. Burdennyy, Vitaly I. Loginov, Irina V. Pronina, Svetlana S. Lukina, Alexey A. Dmitriev and Eleonora A. Braga
Int. J. Mol. Sci. 2021, 22(13), 6810; https://doi.org/10.3390/ijms22136810 - 24 Jun 2021
Cited by 42 | Viewed by 5182
Abstract
Long noncoding RNAs (lncRNAs) have been identified as contributors to the development and progression of cancer through various functions and mechanisms. LncRNA GAS5 is downregulated in multiple cancers and acts as a tumor suppressor in breast cancer. GAS5 interacts with various proteins (e.g., [...] Read more.
Long noncoding RNAs (lncRNAs) have been identified as contributors to the development and progression of cancer through various functions and mechanisms. LncRNA GAS5 is downregulated in multiple cancers and acts as a tumor suppressor in breast cancer. GAS5 interacts with various proteins (e.g., E2F1, EZH2, and YAP), DNA (e.g., the insulin receptor promoter), and various microRNAs (miRNAs). In breast cancer, GAS5 binds with miR-21, miR-222, miR-221-3p, miR-196a-5p, and miR-378a-5p that indicates the presence of several elements for miRNA binding (MREs) in GAS5. Mediated by the listed miRNAs, GAS5 is involved in the upregulation of a number of mRNAs of suppressor proteins such as PTEN, PDCD4, DKK2, FOXO1, and SUFU. Furthermore, the aberrant promoter methylation is involved in the regulation of GAS5 gene expression in triple-negative breast cancer and some other carcinomas. GAS5 can stimulate apoptosis in breast cancer via diverse pathways, including cell death receptors and mitochondrial signaling pathways. GAS5 is also a key player in the regulation of some crucial signal pathways in breast cancer, such as PI3K/AKT/mTOR, Wnt/β-catenin, and NF-κB signaling. Through epigenetic and other mechanisms, GAS5 can increase sensitivity to multiple drugs and improve prognosis. GAS5 is thus a promising target in the treatment of breast cancer patients. Full article
(This article belongs to the Special Issue Non-coding RNA (ncRNA) in Cancer)
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16 pages, 14872 KiB  
Review
An Overview of the Role of Long Non-Coding RNAs in Human Choriocarcinoma
by Riccardo Di Fiore, Sherif Suleiman, Ana Felix, Sharon A. O’Toole, John J. O’Leary, Mark P. Ward, James Beirne, Maja Sabol, Petar Ozretić, Angel Yordanov, Mariela Vasileva-Slaveva, Stoyan Kostov, Margarita Nikolova, Ian Said-Huntingford, Duncan Ayers, Bridget Ellul, Francesca Pentimalli, Antonio Giordano and Jean Calleja-Agius
Int. J. Mol. Sci. 2021, 22(12), 6506; https://doi.org/10.3390/ijms22126506 - 17 Jun 2021
Cited by 9 | Viewed by 4789
Abstract
Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation [...] Read more.
Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. A therapeutic approach is highly effective in patients with early-stage CC. The advanced stage of the disease also has a good prognosis with around 95% of patients cured following chemotherapy. However, advancements in diagnosis and treatment are always needed to improve outcomes for patients with CC. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. Furthermore, detection of cancer-associated lncRNAs in body fluids, such as blood, saliva, and urine of cancer patients, is emerging as a novel method for cancer diagnosis. Although there is evidence for the potential role of lncRNAs in a number of cancers of the female genital tract, their role in CC is poorly understood. This review summarizes the current knowledge of lncRNAs in gestational CC and how this may be applied to future therapeutic strategies in the treatment of this rare cancer. Full article
(This article belongs to the Special Issue Non-coding RNA (ncRNA) in Cancer)
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37 pages, 3229 KiB  
Review
Breast Cancer and the Other Non-Coding RNAs
by Dana Dvorská, Dušan Braný, Marcela Ňachajová, Erika Halašová and Zuzana Danková
Int. J. Mol. Sci. 2021, 22(6), 3280; https://doi.org/10.3390/ijms22063280 - 23 Mar 2021
Cited by 17 | Viewed by 4309
Abstract
Breast cancer is very heterogenous and the most common gynaecological cancer, with various factors affecting its development. While its impact on human lives and national health budgets is still rising in almost all global areas, many molecular mechanisms affecting its onset and development [...] Read more.
Breast cancer is very heterogenous and the most common gynaecological cancer, with various factors affecting its development. While its impact on human lives and national health budgets is still rising in almost all global areas, many molecular mechanisms affecting its onset and development remain unclear. Conventional treatments still prove inadequate in some aspects, and appropriate molecular therapeutic targets are required for improved outcomes. Recent scientific interest has therefore focused on the non-coding RNAs roles in tumour development and their potential as therapeutic targets. These RNAs comprise the majority of the human transcript and their broad action mechanisms range from gene silencing to chromatin remodelling. Many non-coding RNAs also have altered expression in breast cancer cell lines and tissues, and this is often connected with increased proliferation, a degraded extracellular environment, and higher endothelial to mesenchymal transition. Herein, we summarise the known abnormalities in the function and expression of long non-coding RNAs, Piwi interacting RNAs, small nucleolar RNAs and small nuclear RNAs in breast cancer, and how these abnormalities affect the development of this deadly disease. Finally, the use of RNA interference to suppress breast cancer growth is summarised. Full article
(This article belongs to the Special Issue Non-coding RNA (ncRNA) in Cancer)
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