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18 pages, 3065 KiB

Open AccessEditor’s ChoiceArticle

Environmental and Lifestyle Cancer Risk Factors: Shaping Extracellular Vesicle OncomiRs and Paving the Path to Cancer Development

by Valentina Bollati, Paola Monti, Davide Biganzoli, Giuseppe Marano, Chiara Favero, Simona Iodice, Luca Ferrari, Laura Dioni, Francesca Bianchi, Angela Cecilia Pesatori and Elia Mario Biganzoli

Cancers 2023, 15(17), 4317; https://doi.org/10.3390/cancers15174317 - 29 Aug 2023

Cited by 3 | Viewed by 1786

Abstract

Intercellular communication has been transformed by the discovery of extracellular vesicles (EVs) and their cargo, including microRNAs (miRNAs), which play crucial roles in intercellular signaling. These EVs were previously disregarded as cellular debris but are now recognized as vital mediators of biological information [...] Read more.

Intercellular communication has been transformed by the discovery of extracellular vesicles (EVs) and their cargo, including microRNAs (miRNAs), which play crucial roles in intercellular signaling. These EVs were previously disregarded as cellular debris but are now recognized as vital mediators of biological information transfer between cells. Furthermore, they respond not only to internal stimuli but also to environmental and lifestyle factors. Identifying EV-borne oncomiRs, a subset of miRNAs implicated in cancer development, could revolutionize our understanding of how environmental and lifestyle exposures contribute to oncogenesis. To investigate this, we studied the plasma levels of EV-borne oncomiRs in a population of 673 women and 238 men with a body mass index > 25 kg/m² (SPHERE population). The top fifty oncomiRs associated with the three most common cancers in women (breast, colorectal, and lung carcinomas) and men (lung, prostate, and colorectal carcinomas) were selected from the OncomiR database. Only oncomiRs expressed in more than 20% of the population were considered for statistical analysis. Using a Multivariate Adaptive Regression Splines (MARS) model, we explored the interactions between environmental/lifestyle exposures and EV oncomiRs to develop optimized predictor combinations for each EV oncomiR. This innovative approach allowed us to better understand miRNA regulation in response to multiple environmental and lifestyle influences. By uncovering non-linear relationships among variables, we gained valuable insights into the complexity of miRNA regulatory networks. Ultimately, this research paves the way for comprehensive exposome studies in the future. Full article

(This article belongs to the Special Issue Non-coding RNAs and Extracellular Vesicles in Cancer Crosstalk: Diagnostic and Therapeutic Implications)

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22 pages, 1508 KiB

Open AccessReview

Extracellular Vesicles in Lung Cancer: Implementation in Diagnosis and Therapeutic Perspectives

by Anna Paola Carreca, Rosaria Tinnirello, Vitale Miceli, Antonio Galvano, Valerio Gristina, Lorena Incorvaia, Mariangela Pampalone, Simona Taverna and Gioacchin Iannolo

Cancers 2024, 16(11), 1967; https://doi.org/10.3390/cancers16111967 - 22 May 2024

Cited by 2 | Viewed by 1229

Abstract

Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest in finding early diagnostic tools and novel therapeutic approaches, one of which is extracellular vesicles (EVs). EVs are [...] Read more.

Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest in finding early diagnostic tools and novel therapeutic approaches, one of which is extracellular vesicles (EVs). EVs are nanoscale membranous particles that can carry proteins, lipids, and nucleic acids (DNA and RNA), mediating various biological processes, especially in cell–cell communication. As such, they represent an interesting biomarker for diagnostic analysis that can be performed easily by liquid biopsy. Moreover, their growing dataset shows promising results as drug delivery cargo. The aim of our work is to summarize the recent advances in and possible implications of EVs for early diagnosis and innovative therapies for lung cancer. Full article

(This article belongs to the Special Issue Non-coding RNAs and Extracellular Vesicles in Cancer Crosstalk: Diagnostic and Therapeutic Implications)

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22 pages, 1067 KiB

Open AccessReview

Extracellular Vesicle-Related Non-Coding RNAs in Hepatocellular Carcinoma: An Overview

by Giuseppa Augello, Alessandra Cusimano, Melchiorre Cervello and Antonella Cusimano

Cancers 2024, 16(7), 1415; https://doi.org/10.3390/cancers16071415 - 4 Apr 2024

Cited by 1 | Viewed by 1713

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is a major public health problem worldwide, and it is often diagnosed at advanced stages, when no effective treatment options are available. Extracellular vesicles (EVs) are nanosized double-layer lipid vesicles containing various [...] Read more.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is a major public health problem worldwide, and it is often diagnosed at advanced stages, when no effective treatment options are available. Extracellular vesicles (EVs) are nanosized double-layer lipid vesicles containing various biomolecule cargoes, such as lipids, proteins, and nucleic acids. EVs are released from nearly all types of cells and have been shown to play an important role in cell-to-cell communication. In recent years, many studies have investigated the role of EVs in cancer, including HCC. Emerging studies have shown that EVs play primary roles in the development and progression of cancer, modulating tumor growth and metastasis formation. Moreover, it has been observed that non-coding RNAs (ncRNAs) carried by tumor cell-derived EVs promote tumorigenesis, regulating the tumor microenvironment (TME) and playing critical roles in the progression, angiogenesis, metastasis, immune escape, and drug resistance of HCC. EV-related ncRNAs can provide information regarding disease status, thus encompassing a role as biomarkers. In this review, we discuss the main roles of ncRNAs present in HCC-derived EVs, including micro(mi) RNAs, long non-coding (lnc) RNAs, and circular (circ) RNAs, and their potential clinical value as biomarkers and therapeutic targets. Full article

(This article belongs to the Special Issue Non-coding RNAs and Extracellular Vesicles in Cancer Crosstalk: Diagnostic and Therapeutic Implications)

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20 pages, 349 KiB

Open AccessReview

Exploring the Potential of Non-Coding RNAs as Liquid Biopsy Biomarkers for Lung Cancer Screening: A Literature Review

by Edoardo Garbo, Benedetta Del Rio, Giorgia Ferrari, Massimiliano Cani, Valerio Maria Napoli, Valentina Bertaglia, Enrica Capelletto, Christian Rolfo, Silvia Novello and Francesco Passiglia

Cancers 2023, 15(19), 4774; https://doi.org/10.3390/cancers15194774 - 28 Sep 2023

Cited by 2 | Viewed by 1361

Abstract

Lung cancer represent the leading cause of cancer mortality, so several efforts have been focused on the development of a screening program. To address the issue of high overdiagnosis and false positive rates associated to LDCT-based screening, there is a need for new [...] Read more.

Lung cancer represent the leading cause of cancer mortality, so several efforts have been focused on the development of a screening program. To address the issue of high overdiagnosis and false positive rates associated to LDCT-based screening, there is a need for new diagnostic biomarkers, with liquid biopsy ncRNAs detection emerging as a promising approach. In this scenario, this work provides an updated summary of the literature evidence about the role of non-coding RNAs in lung cancer screening. A literature search on PubMed was performed including studies which investigated liquid biopsy non-coding RNAs biomarker lung cancer patients and a control cohort. Micro RNAs were the most widely studied biomarkers in this setting but some preliminary evidence was found also for other non-coding RNAs, suggesting that a multi-biomarker based liquid biopsy approach could enhance their efficacy in the screening context. However, further studies are needed in order to optimize detection techniques as well as diagnostic accuracy before introducing novel biomarkers in the early diagnosis setting. Full article

(This article belongs to the Special Issue Non-coding RNAs and Extracellular Vesicles in Cancer Crosstalk: Diagnostic and Therapeutic Implications)

17 pages, 621 KiB

Open AccessReview

Cystic Fibrosis and Cancer: Unraveling the Complex Role of CFTR Gene in Cancer Susceptibility

by Giuseppe Fabio Parisi, Maria Papale, Giulia Pecora, Novella Rotolo, Sara Manti, Giovanna Russo and Salvatore Leonardi

Cancers 2023, 15(17), 4244; https://doi.org/10.3390/cancers15174244 - 24 Aug 2023

Cited by 2 | Viewed by 2853

Abstract

Cystic fibrosis (CF) is a genetic disorder affecting multiple organs, primarily the lungs and digestive system. Over the years, advancements in medical care and treatments have significantly increased the life expectancy of individuals with CF. However, with this improved longevity, concerns about the [...] Read more.

Cystic fibrosis (CF) is a genetic disorder affecting multiple organs, primarily the lungs and digestive system. Over the years, advancements in medical care and treatments have significantly increased the life expectancy of individuals with CF. However, with this improved longevity, concerns about the potential risk of developing certain types of cancers have arisen. This narrative review aims to explore the relationship between CF, increased life expectancy, and the associated risk for cancers. We discuss the potential mechanisms underlying this risk, including chronic inflammation, immune system dysregulation, and genetic factors. Additionally, we review studies that have examined the incidence and types of cancers seen in CF patients, with a focus on gastrointestinal, breast, and respiratory malignancies. We also explore the impact of CFTR modulator therapies on cancer risk. In the gastrointestinal tract, CF patients have an elevated risk of developing colorectal cancer, pancreatic cancer, and possibly esophageal cancer. The underlying mechanisms contributing to these increased risks are not fully understood, but chronic inflammation, altered gut microbiota, and genetic factors are believed to play a role. Regular surveillance and colonoscopies are recommended for early detection and management of colorectal cancer in CF patients. Understanding the factors contributing to cancer development in CF patients is crucial for implementing appropriate surveillance strategies and improving long-term outcomes. Further research is needed to elucidate the molecular mechanisms involved and develop targeted interventions to mitigate cancer risk in individuals with CF. Full article

(This article belongs to the Special Issue Non-coding RNAs and Extracellular Vesicles in Cancer Crosstalk: Diagnostic and Therapeutic Implications)

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19 pages, 2643 KiB

Open AccessReview

PIWI-RNAs Small Noncoding RNAs with Smart Functions: Potential Theranostic Applications in Cancer

by Simona Taverna, Anna Masucci and Giuseppe Cammarata

Cancers 2023, 15(15), 3912; https://doi.org/10.3390/cancers15153912 - 1 Aug 2023

Cited by 5 | Viewed by 1781

Abstract

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of small noncoding RNAs (ncRNAs) that bind components of the PIWI protein family. piRNAs are specifically expressed in different human tissues and regulate important signaling pathways. Aberrant expressions of piRNAs and PIWI proteins [...] Read more.

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of small noncoding RNAs (ncRNAs) that bind components of the PIWI protein family. piRNAs are specifically expressed in different human tissues and regulate important signaling pathways. Aberrant expressions of piRNAs and PIWI proteins have been associated with tumorigenesis and cancer progression. Recent studies reported that piRNAs are contained in extracellular vesicles (EVs), nanosized lipid particles, with key roles in cell–cell communication. EVs contain several bioactive molecules, such as proteins, lipids, and nucleic acids, including emerging ncRNAs. EVs are one of the components of liquid biopsy (LB) a non-invasive method for detecting specific molecular biomarkers in liquid samples. LB could become a crucial tool for cancer diagnosis with piRNAs as biomarkers in a precision oncology approach. This review summarizes the current findings on the roles of piRNAs in different cancer types, focusing on potential theranostic applications of piRNAs contained in EVs (EV-piRNAs). Their roles as non-invasive diagnostic and prognostic biomarkers and as new therapeutic options have been also discussed. Full article

(This article belongs to the Special Issue Non-coding RNAs and Extracellular Vesicles in Cancer Crosstalk: Diagnostic and Therapeutic Implications)

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25 pages, 1551 KiB

Open AccessReview

Modulating Effects of Cancer-Derived Exosomal miRNAs and Exosomal Processing by Natural Products

by Ya-Ting Chuang, Jen-Yang Tang, Jun-Ping Shiau, Ching-Yu Yen, Fang-Rong Chang, Kun-Han Yang, Ming-Feng Hou, Ammad Ahmad Farooqi and Hsueh-Wei Chang

Cancers 2023, 15(1), 318; https://doi.org/10.3390/cancers15010318 - 3 Jan 2023

Cited by 6 | Viewed by 2749

Abstract

Cancer-derived exosomes exhibit sophisticated functions, such as proliferation, apoptosis, migration, resistance, and tumor microenvironment changes. Several clinical drugs modulate these exosome functions, but the impacts of natural products are not well understood. Exosome functions are regulated by exosome processing, such as secretion and [...] Read more.

Cancer-derived exosomes exhibit sophisticated functions, such as proliferation, apoptosis, migration, resistance, and tumor microenvironment changes. Several clinical drugs modulate these exosome functions, but the impacts of natural products are not well understood. Exosome functions are regulated by exosome processing, such as secretion and assembly. The modulation of these exosome-processing genes can exert the anticancer and precancer effects of cancer-derived exosomes. This review focuses on the cancer-derived exosomal miRNAs that regulate exosome processing, acting on the natural-product-modulating cell functions of cancer cells. However, the role of exosomal processing has been overlooked in several studies of exosomal miRNAs and natural products. In this study, utilizing the bioinformatics database (miRDB), the exosome-processing genes of natural-product-modulated exosomal miRNAs were predicted. Consequently, several natural drugs that modulate exosome processing and exosomal miRNAs and regulate cancer cell functions are described here. This review sheds light on and improves our understanding of the modulating effects of exosomal miRNAs and their potential exosomal processing targets on anticancer treatments based on the use of natural products. Full article

(This article belongs to the Special Issue Non-coding RNAs and Extracellular Vesicles in Cancer Crosstalk: Diagnostic and Therapeutic Implications)

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19 pages, 1793 KiB

Open AccessReview

Non-Coding RNAs in Airway Diseases: A Brief Overview of Recent Data

by Giusy Daniela Albano, Rosalia Gagliardo, Angela Marina Montalbano and Mirella Profita

Cancers 2023, 15(1), 54; https://doi.org/10.3390/cancers15010054 - 22 Dec 2022

Cited by 7 | Viewed by 1977

Abstract

Inflammation of the human lung is mediated in response to different stimuli (e.g., physical, radioactive, infective, pro-allergenic, or toxic) such as cigarette smoke and environmental pollutants. These stimuli often promote an increase in different inflammatory activities in the airways, manifesting themselves as chronic [...] Read more.

Inflammation of the human lung is mediated in response to different stimuli (e.g., physical, radioactive, infective, pro-allergenic, or toxic) such as cigarette smoke and environmental pollutants. These stimuli often promote an increase in different inflammatory activities in the airways, manifesting themselves as chronic diseases (e.g., allergic airway diseases, asthma chronic bronchitis/chronic obstructive pulmonary disease, or even lung cancer). Non-coding RNA (ncRNAs) are single-stranded RNA molecules of few nucleotides that regulate the gene expression involved in many cellular processes. ncRNA are molecules typically involved in the reduction of translation and stability of the genes of mRNAs s. They regulate many biological aspects such as cellular growth, proliferation, differentiation, regulation of cell cycle, aging, apoptosis, metabolism, and neuronal patterning, and influence a wide range of biologic processes essential for the maintenance of cellular homeostasis. The relevance of ncRNAs in the pathogenetic mechanisms of respiratory diseases has been widely established and in the last decade many papers were published. However, once their importance is established in pathogenetic mechanisms, it becomes important to further deepen the research in this direction. In this review we describe several of most recent knowledge concerning ncRNA (overall miRNAs) expression and activities in the lung. Full article

(This article belongs to the Special Issue Non-coding RNAs and Extracellular Vesicles in Cancer Crosstalk: Diagnostic and Therapeutic Implications)

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