Special Issue "Role of miRNAs in Cancer—Analysis of Their Targetome"

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

Deadline for manuscript submissions: 31 March 2020.

Special Issue Editor

Guest Editor
Dr. Alfons Navarro

Molecular Oncology and Embryology Laboratory, Department of Surgery and Surgical Specializations, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
Website | E-Mail
Interests: noncoding RNAs; microRNAs; piwiRNAs; lncRNAs; circularRNAs; extracellular vesicles; exosomes; biomarkers; lung cancer; colorectal cancer; lymphoma; leukemia

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 papers will be 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 monthly 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

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

Published Papers (2 papers)

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Research

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Open AccessArticle
Mir526b and Mir655 Promote Tumour Associated Angiogenesis and Lymphangiogenesis in Breast Cancer
Cancers 2019, 11(7), 938; https://doi.org/10.3390/cancers11070938
Received: 11 June 2019 / Revised: 27 June 2019 / Accepted: 29 June 2019 / Published: 4 July 2019
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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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Open AccessReview
MicroRNA-361: A Multifaceted Player Regulating Tumor Aggressiveness and Tumor Microenvironment Formation
Cancers 2019, 11(8), 1130; https://doi.org/10.3390/cancers11081130
Received: 8 July 2019 / Revised: 1 August 2019 / Accepted: 1 August 2019 / Published: 7 August 2019
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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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