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Cancers
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Role of miRNAs in Cancer—Analysis of Their Targetome
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Role of miRNAs in Cancer—Analysis of Their Targetome

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 56861

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Alfons Navarro

E-Mail Website
Guest Editor
1. Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, Department of Surgery and Surgical Specializations, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
2. August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain
3. Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain
Interests: noncoding RNAs; microRNAs; piwiRNAs; lncRNAs; circularRNAs; extracellular vesicles; exosomes; biomarkers; lung cancer; colorectal cancer; lymphoma; leukemia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is now becoming increasingly apparent that the nonprotein-coding portion of the genome is of crucial functional importance, both for normal physiology and for disease. MicroRNAs (miRNAs) are the best studied noncoding RNA sequences of our genome. Since the discovery of the second miRNA sequence, let-7a, in 2000, the identification of new miRNAs has increased considerably. In fact, as of 2019, we know of more than 2675 mature miRNAs in humans (according to miRBase v22.1). The first evidence that miRNAs were related to cancer also came from let-7a, which was described as a tumor suppressor in 2002. Since then, it has become clear that miRNA expression is dysregulated in human cancers. In order to identify the functions of the dysregulated miRNAs, it is necessary to decipher their target genes. Although multiple individual miRNA targets have been identified, very few studies have evaluated the targetome of specific miRNAs, which would provide us with a broader vision. Moreover, several studies have recently reported that miRNAs also target other noncoding RNAs, playing an important regulatory role of the noncoding RNA compartment. Finally, miRNAs have been shown to play a role not only in tumor cells but also in other cells, where they are transported through exosomes. The screening of exosomal miRNAs and the evaluation of their functions outside the tumor warrant further study to clarify the importance of these extracellular miRNAs in tumor progression and especially in metastasis. The identifications of their targets will also be crucial.

More efforts are still needed to decipher the critical targets—both coding and noncoding RNAs—of the miRNAs involved in cancer and to identify their contribution to malignant transformation and metastasis. The present issue will focus on the identification of the functions of tumorigenic miRNAs through the study of their targetome in both tumor and nontumor cells, where they are transported through exosomes. The large-scale identification of miRNA targets will allow a greater understanding of the complex networks regulated by miRNAs.

Dr. Alfons Navarro
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 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

  • microRNAs
  • targetome
  • AGO-CLIP
  • deep sequencing
  • exosomes
  • extracellular vesicles

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Published Papers (15 papers)

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Editorial

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4 pages, 180 KiB  
Editorial
Deciphering miRNA–Target Relationships to Understand miRNA-Mediated Carcinogenesis
by Alfons Navarro
Cancers 2021, 13(10), 2415; https://doi.org/10.3390/cancers13102415 - 17 May 2021
Cited by 2 | Viewed by 1463
Abstract
We now accept that the non-coding part of the genome is essential for fine-tuning most cellular functions, and that its deregulation drives carcinogenesis [...] Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)

Research

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20 pages, 1069 KiB  
Article
The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer
by Lily Nguyen, Daniela Schilling, Sophie Dobiasch, Susanne Raulefs, Marina Santiago Franco, Dominik Buschmann, Michael W. Pfaffl, Thomas E. Schmid and Stephanie E. Combs
Cancers 2020, 12(12), 3703; https://doi.org/10.3390/cancers12123703 - 9 Dec 2020
Cited by 15 | Viewed by 3269
Abstract
Today, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a five-year overall survival rate of less than 7%. Only 15–20% of patients are eligible for curative intent surgery at the time of diagnosis. Therefore, neoadjuvant treatment regimens have been [...] Read more.
Today, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a five-year overall survival rate of less than 7%. Only 15–20% of patients are eligible for curative intent surgery at the time of diagnosis. Therefore, neoadjuvant treatment regimens have been introduced in order to downsize the tumor by chemotherapy and radiotherapy. To further increase the efficacy of radiotherapy, novel molecular biomarkers are urgently needed to define the subgroup of pancreatic cancer patients who would benefit most from radiotherapy. MicroRNAs (miRNAs) could have the potential to serve as novel predictive and prognostic biomarkers in patients with pancreatic cancer. In the present article, the role of miRNAs as blood biomarkers, which are associated with either radioresistance or radiation-induced changes of miRNAs in pancreatic cancer, is discussed. Furthermore, the manuscript provides own data of miRNAs identified in a pancreatic cancer mouse model as well as radiation-induced miRNA changes in the plasma of tumor-bearing mice. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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18 pages, 2315 KiB  
Article
MiR-378a-3p Is Critical for Burkitt Lymphoma Cell Growth
by Fubiao Niu, Agnieszka Dzikiewicz-Krawczyk, Jasper Koerts, Debora de Jong, Laura Wijenberg, Margot Fernandez Hernandez, Izabella Slezak-Prochazka, Melanie Winkle, Wierd Kooistra, Tineke van der Sluis, Bea Rutgers, Miente Martijn Terpstra, Klaas Kok, Joost Kluiver and Anke van den Berg
Cancers 2020, 12(12), 3546; https://doi.org/10.3390/cancers12123546 - 27 Nov 2020
Cited by 14 | Viewed by 3415
Abstract
MicroRNAs (miRNAs) are small RNA molecules with important gene regulatory roles in normal and pathophysiological cellular processes. Burkitt lymphoma (BL) is an MYC-driven lymphoma of germinal center B (GC-B) cell origin. To gain further knowledge on the role of miRNAs in the pathogenesis [...] Read more.
MicroRNAs (miRNAs) are small RNA molecules with important gene regulatory roles in normal and pathophysiological cellular processes. Burkitt lymphoma (BL) is an MYC-driven lymphoma of germinal center B (GC-B) cell origin. To gain further knowledge on the role of miRNAs in the pathogenesis of BL, we performed small RNA sequencing in BL cell lines and normal GC-B cells. This revealed 26 miRNAs with significantly different expression levels. For five miRNAs, the differential expression pattern was confirmed in primary BL tissues compared to GC-B cells. MiR-378a-3p was upregulated in BL, and its inhibition reduced the growth of multiple BL cell lines. RNA immunoprecipitation of Argonaute 2 followed by microarray analysis (Ago2-RIP-Chip) upon inhibition and ectopic overexpression of miR-378a-3p revealed 63 and 20 putative miR-378a-3p targets, respectively. Effective targeting by miR-378a-3p was confirmed by luciferase reporter assays for MAX Network Transcriptional Repressor (MNT), Forkhead Box P1 (FOXP1), Interleukin 1 Receptor Associated Kinase 4 (IRAK4), and lncRNA Just Proximal To XIST (JPX), and by Western blot for IRAK4 and MNT. Overexpression of IRAK4 and MNT phenocopied the effect of miR-378a-3p inhibition. In summary, we identified miR-378a-3p as a miRNA with an oncogenic role in BL and identified IRAK4 and MNT as miR-378a-3p target genes that are involved in its growth regulatory role. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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11 pages, 1786 KiB  
Communication
Gathering Novel Circulating Exosomal microRNA in Osteosarcoma Cell Lines and Possible Implications for the Disease
by Nicola Cuscino, Lavinia Raimondi, Angela De Luca, Claudia Carcione, Giovanna Russelli, Laura Conti, Jacopo Baldi, Pier Giulio Conaldi, Gianluca Giavaresi and Alessia Gallo
Cancers 2019, 11(12), 1924; https://doi.org/10.3390/cancers11121924 - 3 Dec 2019
Cited by 18 | Viewed by 2840
Abstract
One of the goals of personalized medicine is to understand and treat diseases with greater precision through the molecular profile of the patient. This profiling is becoming a powerful tool for the discovery of novel biomarkers that can guide physicians in assessing, in [...] Read more.
One of the goals of personalized medicine is to understand and treat diseases with greater precision through the molecular profile of the patient. This profiling is becoming a powerful tool for the discovery of novel biomarkers that can guide physicians in assessing, in advance, the disease stage, and monitoring disease progression. Circulating miRNAs and exosomal miRNAs, a group of small non-coding RNAs, are considered the gold standard diagnostic biomarkers for human diseases. We have previously demonstrated that osteosarcoma-derived exosomes are able to influence crucial mechanisms inside tumor niches, inducing osteoclast differentiation, and sustaining bone resorption activity. Here we discovered, through Next-Generation Sequencing (NGS), eight novel microRNAs in three different osteosarcoma cell lines, and assessed the selective packaging into the exosomes released. We then investigated, as proof-of-principle, the presence of the novel microRNAs in osteosarcoma patient samples, and found that 5 of the 8 novel microRNAs were more present in circulating exosomes of osteosarcoma patients compared with the controls. These results raise a question: Could the 8 novel microRNAs play a role for osteosarcoma pathogenesis? Although still premature, the results are encouraging, and further studies with a validation in a larger cohort are needed. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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21 pages, 4669 KiB  
Article
Transcription Factor and miRNA Interplays Can Manifest the Survival of ccRCC Patients
by Shijie Qin, Xuejia Shi, Canbiao Wang, Ping Jin and Fei Ma
Cancers 2019, 11(11), 1668; https://doi.org/10.3390/cancers11111668 - 28 Oct 2019
Cited by 48 | Viewed by 4504
Abstract
Clear cell renal cell carcinoma (ccRCC) still remains a higher mortality rate in worldwide. Obtaining promising biomakers is very crucial for improving the diagnosis and prognosis of ccRCC patients. Herein, we firstly identified eight potentially prognostic miRNAs (hsa-miR-144-5p, hsa-miR-223-3p, hsa-miR-365b-3p, hsa-miR-3613-5p, hsa-miR-9-5p, hsa-miR-183-5p, [...] Read more.
Clear cell renal cell carcinoma (ccRCC) still remains a higher mortality rate in worldwide. Obtaining promising biomakers is very crucial for improving the diagnosis and prognosis of ccRCC patients. Herein, we firstly identified eight potentially prognostic miRNAs (hsa-miR-144-5p, hsa-miR-223-3p, hsa-miR-365b-3p, hsa-miR-3613-5p, hsa-miR-9-5p, hsa-miR-183-5p, hsa-miR-335-3p, hsa-miR-1269a). Secondly, we found that a signature containing these eight miRNAs showed obviously superior to a single miRNA in the prognostic effect and credibility for predicting the survival of ccRCC patients. Thirdly, we discovered that twenty-two transcription factors (TFs) interact with these eight miRNAs, and a signature combining nine TFs (TFAP2A, KLF5, IRF1, RUNX1, RARA, GATA3, IKZF1, POU2F2, and FOXM1) could promote the prognosis of ccRCC patients. Finally, we further identified eleven genes (hsa-miR-365b-3p, hsa-miR-223-3p, hsa-miR-1269a, hsa-miR-144-5p, hsa-miR-183-5p, hsa-miR-335-3p, TFAP2A, KLF5, IRF1, MYC, IKZF1) that could combine as a signature to improve the prognosis effect of ccRCC patients, which distinctly outperformed the eight-miRNA signature and the nine-TF signature. Overall, we identified several new prognosis factors for ccRCC, and revealed a potential mechanism that TFs and miRNAs interplay cooperatively or oppositely regulate a certain number of tumor suppressors, driver genes, and oncogenes to facilitate the survival of ccRCC patients. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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18 pages, 3475 KiB  
Article
MicroRNAs Which Can Prognosticate Aggressiveness of Bladder Cancer
by Edyta Marta Borkowska, Tomasz Konecki, Michał Pietrusiński, Maciej Borowiec and Zbigniew Jabłonowski
Cancers 2019, 11(10), 1551; https://doi.org/10.3390/cancers11101551 - 14 Oct 2019
Cited by 15 | Viewed by 2690
Abstract
Bladder cancer (BC) is still characterized by a very high death rate in patients with this disease. One of the reasons for this is the lack of adequate markers which could help determine the biological potential of the tumor to develop into its [...] Read more.
Bladder cancer (BC) is still characterized by a very high death rate in patients with this disease. One of the reasons for this is the lack of adequate markers which could help determine the biological potential of the tumor to develop into its invasive stage. It has been found that some microRNAs (miRNAs) correlate with disease progression. The purpose of this study was to identify which miRNAs can accurately predict the presence of BC and can differentiate low grade (LG) tumors from high grade (HG) tumors. The study included 55 patients with diagnosed bladder cancer and 30 persons belonging to the control group. The expression of seven selected miRNAs was estimated with the real-time PCR technique according to miR-103-5p (for the normalization of the results). Receiver operating characteristics (ROC) curves and the area under the curve (AUC) were used to evaluate the feasibility of using selected markers as biomarkers for detecting BC and discriminating non-muscle invasive BC (NMIBC) from muscle invasive BC (MIBC). For HG tumors, the relevant classifiers are miR-205-5p and miR-20a-5p, whereas miR-205-5p and miR-182-5p are for LG (AUC = 0.964 and AUC = 0.992, respectively). NMIBC patients with LG disease are characterized by significantly higher miR-130b-3p expression values compared to patients in HG tumors. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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20 pages, 2730 KiB  
Article
Mir526b and Mir655 Promote Tumour Associated Angiogenesis and Lymphangiogenesis in Breast Cancer
by Stephanie Hunter, Braydon Nault, Kingsley Chukwunonso Ugwuagbo, Sujit Maiti and Mousumi Majumder
Cancers 2019, 11(7), 938; https://doi.org/10.3390/cancers11070938 - 4 Jul 2019
Cited by 62 | Viewed by 7259
Abstract
MicroRNAs (miRNAs) are small endogenously produced RNAs, which regulate growth and development, and oncogenic miRNA regulate tumor growth and metastasis. Tumour-associated angiogenesis and lymphangiogenesis are processes involving the release of growth factors from tumour cells into the microenvioronemnt to communicate with endothelial cells [...] Read more.
MicroRNAs (miRNAs) are small endogenously produced RNAs, which regulate growth and development, and oncogenic miRNA regulate tumor growth and metastasis. Tumour-associated angiogenesis and lymphangiogenesis are processes involving the release of growth factors from tumour cells into the microenvioronemnt to communicate with endothelial cells to induce vascular propagation. Here, we examined the roles of cyclo-oxygenase (COX)-2 induced miR526b and miR655 in tumour-associated angiogenesis and lymphangiogenesis. Ectopic overexpression of miR526b and miR655 in poorly metastatic estrogen receptor (ER) positive MCF7 breast cancer cells resulted in upregulation of angiogenesis and lymphangiogenesis markers vascular endothelial growth factor A (VEGFA); VEGFC; VEGFD; COX-2; lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1); and receptors VEGFR1, VEGFR2, and EP4. Further, miRNA-high cell free conditioned media promoted migration and tube formation by human umbilical vein endothelial cells (HUVECs), and upregulated VEGFR1, VEGFR2, and EP4 expression, showing paracrine stimulation of miRNA in the tumor microenvironment. The miRNA-induced migration and tube formation phenotypes were abrogated with EP4 antagonist or PI3K/Akt inhibitor treatments, confirming the involvement of the EP4 and PI3K/Akt pathway. Tumour supressor gene PTEN was found to be downregulated in miRNA high cells, confirming that it is a target of both miRNAs. PTEN inhibits hypoxia-inducible factor-1 (HIF1α) and the PI3K/Akt pathway, and loss of regulation of these pathways through PTEN results in upregulation of VEGF expression. Moreover, in breast tumors, angiogenesis marker VEGFA and lymphangiogenesis marker VEGFD expression was found to be significantly higher compared with non-adjacent control, and expression of miR526b and miR655 was positively correlated with VEGFA, VEGFC, VEGFD, CD31, and LYVE1 expression in breast tumour samples. These findings further strengthen the role of miRNAs as breast cancer biomarkers and EP4 as a potential therapeutic target to abrogate miRNA-induced angiogenesis and lymphangiogenesis in breast cancer. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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Review

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36 pages, 3104 KiB  
Review
Non-Coding RNAs: Uncharted Mediators of Thyroid Cancer Pathogenesis
by Hossein Tabatabaeian, Samantha Peiling Yang and Yvonne Tay
Cancers 2020, 12(11), 3264; https://doi.org/10.3390/cancers12113264 - 4 Nov 2020
Cited by 24 | Viewed by 3393
Abstract
Thyroid cancer is the most prevalent malignancy of the endocrine system and the ninth most common cancer globally. Despite the advances in the management of thyroid cancer, there are critical issues with the diagnosis and treatment of thyroid cancer that result in the [...] Read more.
Thyroid cancer is the most prevalent malignancy of the endocrine system and the ninth most common cancer globally. Despite the advances in the management of thyroid cancer, there are critical issues with the diagnosis and treatment of thyroid cancer that result in the poor overall survival of undifferentiated and metastatic thyroid cancer patients. Recent studies have revealed the role of different non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are dysregulated during thyroid cancer development or the acquisition of resistance to therapeutics, and may play key roles in treatment failure and poor prognosis of the thyroid cancer patients. Here, we systematically review the emerging roles and molecular mechanisms of ncRNAs that regulate thyroid tumorigenesis and drug response. We then propose the potential clinical implications of ncRNAs as novel diagnostic and prognostic biomarkers for thyroid cancer. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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23 pages, 1462 KiB  
Review
Key MicroRNA’s and Their Targetome in Adrenocortical Cancer
by Marthe Chehade, Martyn Bullock, Anthony Glover, Gyorgy Hutvagner and Stan Sidhu
Cancers 2020, 12(8), 2198; https://doi.org/10.3390/cancers12082198 - 6 Aug 2020
Cited by 13 | Viewed by 3416
Abstract
Adrenocortical Carcinoma (ACC) is a rare but aggressive malignancy with poor prognosis and limited response to available systemic therapies. Although complete surgical resection gives the best chance for long-term survival, ACC has a two-year recurrence rate of 50%, which poses a therapeutic challenge. [...] Read more.
Adrenocortical Carcinoma (ACC) is a rare but aggressive malignancy with poor prognosis and limited response to available systemic therapies. Although complete surgical resection gives the best chance for long-term survival, ACC has a two-year recurrence rate of 50%, which poses a therapeutic challenge. High throughput analyses focused on characterizing the molecular signature of ACC have revealed specific micro-RNAs (miRNAs) that are associated with aggressive tumor phenotypes. MiRNAs are small non-coding RNA molecules that regulate gene expression by inhibiting mRNA translation or degrading mRNA transcripts and have been generally implicated in carcinogenesis. This review summarizes the current insights into dysregulated miRNAs in ACC tumorigenesis, their known functions, and specific targetomes. In addition, we explore the possibility of particular miRNAs to be exploited as clinical biomarkers in ACC and as potential therapeutics. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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23 pages, 427 KiB  
Review
The Role of miRNA for the Treatment of MGMT Unmethylated Glioblastoma Multiforme
by Anna Kirstein, Thomas E. Schmid and Stephanie E. Combs
Cancers 2020, 12(5), 1099; https://doi.org/10.3390/cancers12051099 - 28 Apr 2020
Cited by 25 | Viewed by 4813
Abstract
Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than [...] Read more.
Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than 3% and an average survival rate of 12 months after diagnosis, GBM has become a focus of current research to urgently develop new therapeutic approaches in order to prolong survival of GBM patients. The methylation status of the promoter region of the O6-methylguanine–DNA methyltransferase (MGMT) is nowadays routinely analyzed since a methylated promoter region is beneficial for an effective response to temozolomide-based chemotherapy. Furthermore, several miRNAs were identified regulating MGMT expression, apart from promoter methylation, by degrading MGMT mRNA before protein translation. These miRNAs could be a promising innovative treatment approach to enhance Temozolomide (TMZ) sensitivity in MGMT unmethylated patients and to increase progression-free survival as well as long-term survival. In this review, the relevant miRNAs are systematically reviewed. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
18 pages, 2499 KiB  
Review
Viral miRNAs as Active Players and Participants in Tumorigenesis
by Alessia Gallo, Vitale Miceli, Matteo Bulati, Gioacchin Iannolo, Flavia Contino and Pier Giulio Conaldi
Cancers 2020, 12(2), 358; https://doi.org/10.3390/cancers12020358 - 4 Feb 2020
Cited by 25 | Viewed by 3909
Abstract
The theory that viruses play a role in human cancers is now supported by scientific evidence. In fact, around 12% of human cancers, a leading cause of morbidity and mortality in some regions, are attributed to viral infections. However, the molecular mechanism remains [...] Read more.
The theory that viruses play a role in human cancers is now supported by scientific evidence. In fact, around 12% of human cancers, a leading cause of morbidity and mortality in some regions, are attributed to viral infections. However, the molecular mechanism remains complex to decipher. In recent decades, the uncovering of cellular miRNAs, with their invaluable potential as diagnostic and prognostic biomarkers, has increased the number of studies being conducted regarding human cancer diagnosis. Viruses develop clever mechanisms to succeed in the maintenance of the viral life cycle, and some viruses, especially herpesviruses, encode for miRNA, v-miRNAs. Through this viral miRNA, the viruses are able to manipulate cellular and viral gene expression, driving carcinogenesis and escaping the host innate or adaptive immune system. In this review, we have discussed the main viral miRNAs and virally influenced cellular pathways, and their capability to drive carcinogenesis. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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25 pages, 2583 KiB  
Review
Interplay among SNAIL Transcription Factor, MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Regulation of Tumor Growth and Metastasis
by Klaudia Skrzypek and Marcin Majka
Cancers 2020, 12(1), 209; https://doi.org/10.3390/cancers12010209 - 14 Jan 2020
Cited by 41 | Viewed by 4561
Abstract
SNAIL (SNAI1) is a zinc finger transcription factor that binds to E-box sequences and regulates the expression of genes. It usually acts as a gene repressor, but it may also activate the expression of genes. SNAIL plays a key role in the regulation [...] Read more.
SNAIL (SNAI1) is a zinc finger transcription factor that binds to E-box sequences and regulates the expression of genes. It usually acts as a gene repressor, but it may also activate the expression of genes. SNAIL plays a key role in the regulation of epithelial to mesenchymal transition, which is the main mechanism responsible for the progression and metastasis of epithelial tumors. Nevertheless, it also regulates different processes that are responsible for tumor growth, such as the activity of cancer stem cells, the control of cell metabolism, and the regulation of differentiation. Different proteins and microRNAs may regulate the SNAIL level, and SNAIL may be an important regulator of microRNA expression as well. The interplay among SNAIL, microRNAs, long non-coding RNAs, and circular RNAs is a key event in the regulation of tumor growth and metastasis. This review for the first time discusses different types of regulation between SNAIL and non-coding RNAs with a focus on feedback loops and the role of competitive RNA. Understanding these mechanisms may help develop novel therapeutic strategies against cancer based on microRNAs. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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21 pages, 1375 KiB  
Review
MicroRNAs and Metastasis
by Carla Solé and Charles H. Lawrie
Cancers 2020, 12(1), 96; https://doi.org/10.3390/cancers12010096 - 30 Dec 2019
Cited by 15 | Viewed by 3684
Abstract
Metastasis, the development of secondary malignant growths at a distance from the primary site of a cancer, is associated with almost 90% of all cancer deaths, and half of all cancer patients present with some form of metastasis at the time of diagnosis. [...] Read more.
Metastasis, the development of secondary malignant growths at a distance from the primary site of a cancer, is associated with almost 90% of all cancer deaths, and half of all cancer patients present with some form of metastasis at the time of diagnosis. Consequently, there is a clear clinical need for a better understanding of metastasis. The role of miRNAs in the metastatic process is beginning to be explored. However, much is still to be understood. In this review, we present the accumulating evidence for the importance of miRNAs in metastasis as key regulators of this hallmark of cancer. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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Graphical abstract

13 pages, 1448 KiB  
Review
MicroRNA-361: A Multifaceted Player Regulating Tumor Aggressiveness and Tumor Microenvironment Formation
by Daozhi Xu, Peixin Dong, Ying Xiong, Junming Yue, Kei Ihira, Yosuke Konno, Noriko Kobayashi, Yukiharu Todo and Hidemichi Watari
Cancers 2019, 11(8), 1130; https://doi.org/10.3390/cancers11081130 - 7 Aug 2019
Cited by 17 | Viewed by 3445
Abstract
MicroRNA-361-5p (miR-361) expression frequently decreases or is lost in different types of cancers, and contributes to tumor suppression by repressing the expression of its target genes implicated in tumor growth, epithelial-to-mesenchymal transition (EMT), metastasis, drug resistance, glycolysis, angiogenesis, and inflammation. Here, we review [...] Read more.
MicroRNA-361-5p (miR-361) expression frequently decreases or is lost in different types of cancers, and contributes to tumor suppression by repressing the expression of its target genes implicated in tumor growth, epithelial-to-mesenchymal transition (EMT), metastasis, drug resistance, glycolysis, angiogenesis, and inflammation. Here, we review the expression pattern of miR-361 in human tumors, describe the mechanisms responsible for its dysregulation, and discuss how miR-361 modulates the aggressive properties of tumor cells and alter the tumor microenvironment by acting as a novel tumor suppressor. Furthermore, we describe its potentials as a promising diagnostic or prognostic biomarker for cancers and a promising target for therapeutic development. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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Other

11 pages, 626 KiB  
Perspective
MicroRNAs and Their Targetomes in Tumor-Immune Communication
by Sunglim Cho, Jesse W. Tai and Li-Fan Lu
Cancers 2020, 12(8), 2025; https://doi.org/10.3390/cancers12082025 - 24 Jul 2020
Cited by 9 | Viewed by 2509
Abstract
The development of cancer is a complex and dynamically regulated multiple-step process that involves many changes in gene expression. Over the last decade, microRNAs (miRNAs), a class of short regulatory non-coding RNAs, have emerged as key molecular effectors and regulators of tumorigenesis. While [...] Read more.
The development of cancer is a complex and dynamically regulated multiple-step process that involves many changes in gene expression. Over the last decade, microRNAs (miRNAs), a class of short regulatory non-coding RNAs, have emerged as key molecular effectors and regulators of tumorigenesis. While aberrant expression of miRNAs or dysregulated miRNA-mediated gene regulation in tumor cells have been shown to be capable of directly promoting or inhibiting tumorigenesis, considering the well-reported role of the immune system in cancer, tumor-derived miRNAs could also impact tumor growth through regulating anti-tumor immune responses. Here, we discuss howmiRNAs can function as central mediators that influence the crosstalk between cancer and the immune system. Moreover, we also review the current progress in the development of novel experimental approaches for miRNA target identification that will facilitate our understanding of miRNA-mediated gene regulation in not only human malignancies, but also in other genetic disorders. Full article
(This article belongs to the Special Issue Role of miRNAs in Cancer—Analysis of Their Targetome)
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