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MicroRNA Dysregulation in Tumor Occurrence, Progression and Response to Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 25096

Special Issue Editor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Interests: microRNA; breast cancer; HER2; targeted therapy; prognostic and predictive biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The aberrant deregulation of microRNAs is currently a well-recognized hallmark of human cancer. These small non-coding RNA molecules are functionally involved in different steps of the carcinogenesis process, from occurrence to progression and metastasis. Moreover, they have been related to different sensitivities to a wide range of anti-cancer therapies, from chemotherapeutic compounds to targeted therapies.
Consequently, an aberrant microRNA expression, both in tumors and in circulation, might represent a useful biomarker for early diagnosis, or it could be tracked to monitor disease progression and response to therapies.
Finally, despite the difficulties in translating experimental results into a clinical application, enthusiasm regarding the potential use of microRNAs as tools or targets for an innovative therapy has not faded yet. Indeed, new techniques and approaches for miRNA-based therapies are currently under investigation.
In summary, the topic of this Special Issue can include different aspects of miRNA deregulation in tumors, ranging from basic to more applicative studies:

  • microRNAs are functionally involved in tumor occurrence/progression;
  • microRNAs are functionally involved in the response to anti-cancer therapies;
  • tissue or circulating microRNA deregulation as biomarkers;
  • microRNA modulation as a therapeutic tool.

Dr. Marilena V. Iorio
Guest Editor

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Published Papers (7 papers)

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Editorial

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2 pages, 144 KiB  
Editorial
Editorial to the Special Issue “MicroRNA Dysregulation in Tumor Occurrence, Progression and Response to Therapy”
by Marilena V. Iorio
Int. J. Mol. Sci. 2021, 22(4), 2156; https://doi.org/10.3390/ijms22042156 - 22 Feb 2021
Viewed by 996
Abstract
In the last 20 years, the involvement of microRNAs in the biology of human tumors has been clearly demonstrated, and the scientific community has switched from an initial skepticism to an increasing interest toward what was called the “dark side” of DNA [...] [...] Read more.
In the last 20 years, the involvement of microRNAs in the biology of human tumors has been clearly demonstrated, and the scientific community has switched from an initial skepticism to an increasing interest toward what was called the “dark side” of DNA [...] Full article

Research

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13 pages, 2754 KiB  
Article
Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy
by Serena Di Cosimo, Valentina Appierto, Sara Pizzamiglio, Marco Silvestri, José Baselga, Martine Piccart, Jens Huober, Miguel Izquierdo, Lorena de la Pena, Florentine S. Hilbers, Evandro de Azambuja, Michael Untch, Lajos Pusztai, Kathleen Pritchard, Paolo Nuciforo, Anne Vincent-Salomon, Fraser Symmans, Giovanni Apolone, Filippo G. de Braud, Marilena V. Iorio, Paolo Verderio and Maria Grazia Daidoneadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2020, 21(4), 1386; https://doi.org/10.3390/ijms21041386 - 18 Feb 2020
Cited by 30 | Viewed by 3901
Abstract
Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p [...] Read more.
Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p were significantly associated with pathological complete response (pCR) (p = 0.008 and 0.048, respectively). At a threshold ≥ the upper limit of the 95%CI of the mean difference, pCR resulted 45% (95%CI 24%–68%), and 44% (95%CI 22%–69%) for ct-miR-148a-3p and ct-miR-374a-5p, respectively. Notably, ct-miR-148a-3p retained its predictive value (OR 3.42, 95%CI 1.23–9.46, p = 0.018) in bivariate analysis along with estrogen receptor status. Combined information from ct-miR-148a-3p and ct-miR140-5p, which we previously reported to identify trastuzumab-responsive patients, resulted in greater predictive capability over each other, with pCR of 54% (95%CI 25%–81%) and 0% (95%CI 0%–31%) in ct-miR-148a/ct-miR-140-5p high/present and low/absent, respectively. GO and KEGG analyses showed common enriched terms between the targets of these ct-miRNAs, including cell metabolism regulation, AMPK and MAPK signaling, and HCC progression. In conclusion, early modulated ct-miR-148-3p may inform on the functional processes underlying treatment response, integrate the information from already available predictive biomarkers, and identify patients likely to respond to single agent trastuzumab-based neoadjuvant therapy. Full article
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Review

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12 pages, 565 KiB  
Review
miR-205 in Breast Cancer: State of the Art
by Ilaria Plantamura, Alessandra Cataldo, Giulia Cosentino and Marilena V. Iorio
Int. J. Mol. Sci. 2021, 22(1), 27; https://doi.org/10.3390/ijms22010027 - 22 Dec 2020
Cited by 33 | Viewed by 3456
Abstract
Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the [...] Read more.
Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field. Full article
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18 pages, 1045 KiB  
Review
Non-Coding RNAs as Cancer Hallmarks in Chronic Lymphocytic Leukemia
by Linda Fabris, Jaroslav Juracek and George Calin
Int. J. Mol. Sci. 2020, 21(18), 6720; https://doi.org/10.3390/ijms21186720 - 14 Sep 2020
Cited by 13 | Viewed by 2994
Abstract
The discovery of non-coding RNAs (ncRNAs) and their role in tumor onset and progression has revolutionized the way scientists and clinicians study cancers. This discovery opened new layers of complexity in understanding the fine-tuned regulation of cellular processes leading to cancer. NcRNAs represent [...] Read more.
The discovery of non-coding RNAs (ncRNAs) and their role in tumor onset and progression has revolutionized the way scientists and clinicians study cancers. This discovery opened new layers of complexity in understanding the fine-tuned regulation of cellular processes leading to cancer. NcRNAs represent a heterogeneous group of transcripts, ranging from a few base pairs to several kilobases, that are able to regulate gene networks and intracellular pathways by interacting with DNA, transcripts or proteins. Deregulation of ncRNAs impinge on several cellular responses and can play a major role in each single hallmark of cancer. This review will focus on the most important short and long non-coding RNAs in chronic lymphocytic leukemia (CLL), highlighting their implications as potential biomarkers and therapeutic targets as they relate to the well-established hallmarks of cancer. The key molecular events in the onset of CLL will be contextualized, taking into account the role of the “dark matter” of the genome. Full article
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14 pages, 639 KiB  
Review
Radiosensitization of Hepatocellular Carcinoma through Targeting Radio-Associated MicroRNA
by Cheng-Heng Wu, Cheng-Yi Chen, Chau-Ting Yeh and Kwang-Huei Lin
Int. J. Mol. Sci. 2020, 21(5), 1859; https://doi.org/10.3390/ijms21051859 - 09 Mar 2020
Cited by 18 | Viewed by 3020
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. For patients who are resistant to monotherapy, multimodal therapy is a basic oncologic principle that incorporates surgery, radiotherapy (RT), and chemotherapy providing survival benefits for patients with most types of cancer. [...] Read more.
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. For patients who are resistant to monotherapy, multimodal therapy is a basic oncologic principle that incorporates surgery, radiotherapy (RT), and chemotherapy providing survival benefits for patients with most types of cancer. Although liver has low tolerance for radiation, high-precision RT for local HCC minimizes the likelihood of radiation-induced liver disease (RILD) in noncancerous liver tissue. RT have several therapeutic benefits, including the down-staging of tumors to make them resectable and repression of metastasis. The DNA damage response (DDR) is a cellular response to irradiation (IR), including DNA repair of injured cells and induction of programmed cell death, thereby resulting in maintenance of cell homeostasis. Molecules that block the activity of proteins in DDR pathways have been found to enhance radiotherapeutic effects. These molecules include antibodies, kinase inhibitors, siRNAs and miRNAs. MicroRNAs (miRNAs) are short non-coding regulatory RNAs binding to the 3′-untranslated regions (3′-UTR) of the messenger RNAs (mRNAs) of target genes, regulating their translation and expression of proteins. Thus, miRNAs and their target genes constitute complicated interactive networks, which interact with other molecules during carcinogenesis. Due to their promising roles in carcinogenesis, miRNAs were shown to be the potential factors that mediated radiosensitivity and optimized outcomes of the combination of systemic therapy and radiotherapy. Full article
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27 pages, 2140 KiB  
Review
Cancer-Derived Extracellular Vesicle-Associated MicroRNAs in Intercellular Communication: One Cell’s Trash Is Another Cell’s Treasure
by Joseph Mills, Marina Capece, Emanuele Cocucci, Anna Tessari and Dario Palmieri
Int. J. Mol. Sci. 2019, 20(24), 6109; https://doi.org/10.3390/ijms20246109 - 04 Dec 2019
Cited by 44 | Viewed by 6909
Abstract
Several non-protein-coding genomic regions, previously marked as “junk DNA”, have been reported to be transcriptionally active, giving rise to non-coding RNA species implicated in fundamental biological and pathological processes. In particular, microRNAs (miRNAs), a class of small non-coding RNAs mediating post-transcriptional gene silencing, [...] Read more.
Several non-protein-coding genomic regions, previously marked as “junk DNA”, have been reported to be transcriptionally active, giving rise to non-coding RNA species implicated in fundamental biological and pathological processes. In particular, microRNAs (miRNAs), a class of small non-coding RNAs mediating post-transcriptional gene silencing, are causally involved in several human diseases, including various cancer types. Extracellular vesicles (EVs) are membranous structures physiologically released by most cell types. Initially, they were considered a “waste-removal” mechanism, through which cells could dispose unnecessary material and organelles. It is now widely demonstrated that EVs also play a critical role in intercellular communication, mediating the horizontal transfer of lipids, proteins, and genetic material. A paradigm shift in the biology of miRNAs was represented by the discovery that EVs, especially from cancer cells, contain miRs. EV-associated miRs act as autocrine, paracrine and endocrine factors, participating in cancer pathogenesis by modulating intercellular communication. Noteworthy, these formerly neglected molecules are now considered the next generation of cancer “theranostic” tools, with strong clinical relevance. In this review, we aim to summarize the most recent findings regarding EV-associated miRs in cancer pathogenesis and in the development of novel anti-neoplastic diagnostic and therapeutic approaches. Full article
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13 pages, 1397 KiB  
Review
MiRNAs as Players in Rhabdomyosarcoma Development
by Patrizia Gasparini, Andrea Ferrari, Michela Casanova, Francesca Limido, Maura Massimino, Gabriella Sozzi and Orazio Fortunato
Int. J. Mol. Sci. 2019, 20(22), 5818; https://doi.org/10.3390/ijms20225818 - 19 Nov 2019
Cited by 11 | Viewed by 3361
Abstract
Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma of childhood and adolescence, is a rare but aggressive malignancy that originates from immature mesenchymal cells committed to skeletal muscle differentiation. Although RMS is, generally, responsive to the modern multimodal therapeutic approaches, the prognosis of [...] Read more.
Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma of childhood and adolescence, is a rare but aggressive malignancy that originates from immature mesenchymal cells committed to skeletal muscle differentiation. Although RMS is, generally, responsive to the modern multimodal therapeutic approaches, the prognosis of RMS depends on multiple variables and for some patients the outcome remains dismal. Further comprehension of the molecular and cellular biology of RMS would lead to identification of novel therapeutic targets. MicroRNAs (miRNAs) are small non-coding RNAs proved to function as key regulators of skeletal muscle cell fate determination and to play important roles in RMS pathogenesis. The purpose of this review is to better delineate the role of miRNAs as a biomarkers or functional leaders in RMS development, so to possibly elucidate some of RMS molecular mechanisms and potentially therapeutically target them to improve clinical management of pediatric RMS. Full article
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