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Cancers
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microRNA and Oxidative Drugs in Cancer Therapy and Prevention
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microRNA and Oxidative Drugs in Cancer Therapy and Prevention

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 30394

Special Issue Editors

Prof. Dr. Alberto Izzotti

E-Mail Website
Guest Editor
Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy
Interests: microRNA; epigenetic modulation; cancer; oxidative stress; biomarker; endometrial cancer
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ming You

E-Mail Website
Guest Editor
Center for Disease Prevention Research and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Interests: immunotherapy; oral cancer

Special Issue Information

Dear Colleagues,

The epigenetic control of gene expression is achieved at the postgenomic level in the cytoplasm by microRNA machinery. MicroRNAs are able to intercept and suppress messenger RNAs encoded by mutated oncogenes, thus blocking the progress, spreading, and recurrences of cancer. Indeed, cancer growth occurs only when microRNA machinery is severely damaged. MicroRNA expression can be restored and modulated by the administration of suitable microRNA mimics. This approach is particularly important in cancer stem cells characterized by a peculiar micoRNA profile, quiescent status, and a high abundancy of antioxidants, making these cells resistant to chemo-radiotherapies. In this context, oxidative drugs and inhibition of Nrf2 antioxidant pathways may be proposed as possible strategies to target cancer stem cell and to decrease the probability of cancer relapse.

The goal of this Special Issue is to focus on the clinical applicability of microRNA and oxidative drugs to cancer therapy and prevention. The issue will analyze the status of experimental knowledge in preclinical experimental models as well as the translatability of the obtained results to the clinics. Attention will be focused on advantages and problems limiting the feasibility of applying these new strategies in human patients. Attention will be focused on the use of microRNA and oxidative drugs as complimentary approaches to chemo-radiotherapies in cancer therapy to overcome resistance and in cancer prevention to decrease the risk of relapses. 

Prof. Dr. Alberto Izzotti
Prof. Dr. Ming You
Guest Editors

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

  • microRNA
  • oxidative damage
  • cancer prevention
  • cancer relapses
  • antioxidant depletion
  • cancer stem cells
  • integrated cancer therapy
  • chemoresistance

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review

4 pages, 201 KiB  
Editorial
Oxidative Drugs and microRNA: New Opportunities for Cancer Prevention
by Alberto Izzotti
Cancers 2023, 15(1), 132; https://doi.org/10.3390/cancers15010132 - 26 Dec 2022
Cited by 2 | Viewed by 1557
Abstract
Despite the impressive progress of therapies in recent years, cancer still remains the second leading cause of death in developed countries [...] Full article
(This article belongs to the Special Issue microRNA and Oxidative Drugs in Cancer Therapy and Prevention)

Research

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21 pages, 3689 KiB  
Article
A Circulating Risk Score, Based on Combined Expression of Exo-miR-130a-3p and Fibrinopeptide A, as Predictive Biomarker of Relapse in Resectable Non-Small Cell Lung Cancer Patients
by Silvia Marconi, Michela Croce, Giovanna Chiorino, Giovanni Rossi, Francesca Guana, Aldo Profumo, Paola Ostano, Angela Alama, Luca Longo, Giuseppa De Luca, Mariella Dono, Maria Giovanna Dal Bello, Marco Ponassi, Camillo Rosano, Paolo Romano, Zita Cavalieri, Massimiliano Grassi, Marco Tagliamento, Lodovica Zullo, Consuelo Venturi, Chiara Dellepiane, Luca Mastracci, Elisa Bennicelli, Paolo Pronzato, Carlo Genova and Simona Cocoadd Show full author list remove Hide full author list
Cancers 2022, 14(14), 3412; https://doi.org/10.3390/cancers14143412 - 14 Jul 2022
Cited by 9 | Viewed by 2943
Abstract
To date, the 5-year overall survival rate of 60% for early-stage non-small cell lung cancer (NSCLC) is still unsatisfactory. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on an interconnection between cancer cells and the surrounding tumor [...] Read more.
To date, the 5-year overall survival rate of 60% for early-stage non-small cell lung cancer (NSCLC) is still unsatisfactory. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on an interconnection between cancer cells and the surrounding tumor microenvironment; hence, circulating molecules may represent promising markers of cancer recurrence. In order to identify a prognostic score, we performed in-depth high-throughput analyses of plasma circulating markers, including exosomal microRNAs (Exo-miR) and peptides, in 67 radically resected NSCLCs. The miRnome profile selected the Exo-miR-130a-3p as the most overexpressed in relapsed patients. Peptidome analysis identified four progressively more degraded forms of fibrinopeptide A (FpA), which were depleted in progressing patients. Notably, stepwise Cox regression analysis selected Exo-miR-130a-3p and the greatest FpA (2-16) to build a score predictive of recurrence, where high-risk patients had 18 months of median disease-free survival. Moreover, in vitro transfections showed that higher levels of miR-130a-3p lead to a deregulation of pathways involved in metastasis and angiogenesis, including the coagulation process and metalloprotease increase which might be linked to FpA reduction. In conclusion, by integrating circulating markers, the identified risk score may help clinicians predict early-stage NSCLC patients who are more likely to relapse after primary surgery. Full article
(This article belongs to the Special Issue microRNA and Oxidative Drugs in Cancer Therapy and Prevention)
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18 pages, 6117 KiB  
Article
Chemoprevention of Lung Cancer with a Combination of Mitochondria-Targeted Compounds
by Qi Zhang, Donghai Xiong, Jing Pan, Yian Wang, Micael Hardy, Balaraman Kalyanaraman and Ming You
Cancers 2022, 14(10), 2538; https://doi.org/10.3390/cancers14102538 - 21 May 2022
Cited by 11 | Viewed by 3339
Abstract
Combined treatment targeting mitochondria may improve the efficacy of lung cancer chemoprevention. Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational [...] Read more.
Combined treatment targeting mitochondria may improve the efficacy of lung cancer chemoprevention. Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. All chemopreventive treatments began one-week post-carcinogen treatment and continued daily for 24 weeks. No evidence of toxicity (including liver toxicity) was detected by monitoring serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. Mito-HNK or Mito-LND treatment alone reduced tumor load by 56% and 48%, respectively, whereas the combination of Mito-HNK and Mito-LND reduced tumor load by 83%. To understand the potential mechanism(s) of action for the observed combinatorial effects, single-cell RNA sequencing was performed using mouse tumors treated with Mito-HNK, Mito-LND, and their combination. In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). Therefore, the combination of Mito-HNK with Mito-LND may present an effective strategy for lung cancer chemoprevention. Full article
(This article belongs to the Special Issue microRNA and Oxidative Drugs in Cancer Therapy and Prevention)
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24 pages, 11035 KiB  
Article
Efficacy of High-Ozonide Oil in Prevention of Cancer Relapses Mechanisms and Clinical Evidence
by Alberto Izzotti, Enzo Fracchia, Camillo Rosano, Antonio Comite, Liliana Belgioia, Salvatore Sciacca, Zumama Khalid, Matteo Congiu, Cristina Colarossi, Giusi Blanco, Antonio Santoro, Massimo Chiara and Alessandra Pulliero
Cancers 2022, 14(5), 1174; https://doi.org/10.3390/cancers14051174 - 24 Feb 2022
Cited by 7 | Viewed by 8159
Abstract
Background: Cancer tissue is characterized by low oxygen availability triggering neo angiogenesis and metastatisation. Accordingly, oxidation is a possible strategy for counteracting cancer progression and relapses. Previous studies used ozone gas, administered by invasive methods, both in experimental animals and clinical studies, transiently [...] Read more.
Background: Cancer tissue is characterized by low oxygen availability triggering neo angiogenesis and metastatisation. Accordingly, oxidation is a possible strategy for counteracting cancer progression and relapses. Previous studies used ozone gas, administered by invasive methods, both in experimental animals and clinical studies, transiently decreasing cancer growth. This study evaluated the effect of ozonized oils (administered either topically or orally) on cancer, exploring triggered molecular mechanisms. Methods: In vitro, in lung and glioblastoma cancer cells, ozonized oils having a high ozonide content suppressed cancer cell viability by triggering mitochondrial damage, intracellular calcium release, and apoptosis. In vivo, a total of 115 cancer patients (age 58 ± 14 years; 44 males, 71 females) were treated with ozonized oil as complementary therapy in addition to standard chemo/radio therapeutic regimens for up to 4 years. Results: Cancer diagnoses were brain glioblastoma, pancreas adenocarcinoma, skin epithelioma, lung cancer (small and non-small cell lung cancer), colon adenocarcinoma, breast cancer, prostate adenocarcinoma. Survival rate was significantly improved in cancer patients receiving HOO as integrative therapy as compared with those receiving standard treatment only. Conclusions: These results indicate that ozonized oils at high ozonide may represent an innovation in complementary cancer therapy worthy of further clinical studies. Full article
(This article belongs to the Special Issue microRNA and Oxidative Drugs in Cancer Therapy and Prevention)
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22 pages, 4982 KiB  
Article
Epigenetic Silencing of miR-33b Promotes Peritoneal Metastases of Ovarian Cancer by Modulating the TAK1/FASN/CPT1A/NF-κB Axis
by Xueyu Wang, Mingo M. H. Yung, Rakesh Sharma, Fushun Chen, Ying-Tung Poon, Wai-Yip Lam, Benjamin Li, Hextan Y. S. Ngan, Karen K. L. Chan and David W. Chan
Cancers 2021, 13(19), 4795; https://doi.org/10.3390/cancers13194795 - 24 Sep 2021
Cited by 21 | Viewed by 4097
Abstract
Peritoneal metastases are frequently found in high-grade serous carcinoma (HGSOC) patients and are commonly associated with a poor prognosis. The tumor microenvironment (TME) is a complex milieu that plays a critical role in epigenetic alterations driving tumor development and metastatic progression. However, the [...] Read more.
Peritoneal metastases are frequently found in high-grade serous carcinoma (HGSOC) patients and are commonly associated with a poor prognosis. The tumor microenvironment (TME) is a complex milieu that plays a critical role in epigenetic alterations driving tumor development and metastatic progression. However, the impact of epigenetic alterations on metastatic ovarian cancer cells in the harsh peritoneal microenvironment remains incompletely understood. Here, we identified that miR-33b is frequently silenced by promoter hypermethylation in HGSOC cells derived from metastatic omental tumor tissues. Enforced expression of miR-33b abrogates the oncogenic properties of ovarian cancer cells cocultured in omental conditioned medium (OCM), which mimics the ascites microenvironment, and in vivo tumor growth. Of note, restoration of miR-33b inhibited OCM-upregulated de novo lipogenesis and fatty acid β-oxidation in ovarian cancer cells, indicating that miR-33b may play a novel tumor suppressor role in the lipid-mediated oncogenic properties of metastatic ovarian cancer cells found in the omentum. Mechanistic studies demonstrated that miR-33b directly targets transforming growth factor beta-activated kinase 1 (TAK1), thereby suppressing the activities of fatty acid synthase (FASN) and carnitine palmitoyltransferase 1A (CPT1A) in modulating lipid metabolic activities and simultaneously inhibiting the phosphorylation of NF-κB signaling to govern the oncogenic behaviors of ovarian cancer cells. Thus, our data suggest that a lipid-rich microenvironment may cause epigenetic silencing of miR-33b, which negatively modulates ovarian cancer peritoneal metastases, at least in part, by suppressing TAK1/FASN/CPT1A/NF-κB signaling. Full article
(This article belongs to the Special Issue microRNA and Oxidative Drugs in Cancer Therapy and Prevention)
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Review

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15 pages, 358 KiB  
Review
Oxidative-Stress-Sensitive microRNAs in UV-Promoted Development of Melanoma
by Alessandra Pecorelli and Giuseppe Valacchi
Cancers 2022, 14(13), 3224; https://doi.org/10.3390/cancers14133224 - 30 Jun 2022
Cited by 15 | Viewed by 3185
Abstract
Melanoma is the most aggressive and life-threatening form of skin cancer. Key molecular events underlying the melanocytic transformation into malignant melanoma mainly involve gene mutations in which exposure to ultraviolet (UV) radiation plays a prominent role. However, several aspects of UV-induced melanomagenesis remain [...] Read more.
Melanoma is the most aggressive and life-threatening form of skin cancer. Key molecular events underlying the melanocytic transformation into malignant melanoma mainly involve gene mutations in which exposure to ultraviolet (UV) radiation plays a prominent role. However, several aspects of UV-induced melanomagenesis remain to be explored. Interestingly, redox-mediated signaling and perturbed microRNA (miRNA) profiles appear to be interconnected contributing factors able to act synergistically in melanoma initiation and progression. Since UV radiation can promote both redox imbalance and miRNA dysregulation, a harmful crosstalk between these two key cellular networks, with UV as central hub among them, is likely to occur in skin tissue. Therefore, decoding the complex circuits that orchestrate the interaction of UV exposure, oxidative stress, and dysregulated miRNA profiling can provide a deep understanding of the molecular basis of the melanomagenesis process. Furthermore, these mechanistic insights into the reciprocal regulation between these systems could have relevant implications for future therapeutic approaches aimed at counteracting UV-induced redox and miRNome imbalances for the prevention and treatment of malignant melanoma. In this review, we illustrate current information on the intricate connection between UV-induced dysregulation of redox-sensitive miRNAs and well-known signaling pathways involved in the malignant transformation of normal melanocytes to malignant melanoma. Full article
(This article belongs to the Special Issue microRNA and Oxidative Drugs in Cancer Therapy and Prevention)
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20 pages, 667 KiB  
Review
Circulating miRNAs in Breast Cancer Diagnosis and Prognosis
by Barbara Cardinali, Roberta Tasso, Patrizia Piccioli, Maria Chiara Ciferri, Rodolfo Quarto and Lucia Del Mastro
Cancers 2022, 14(9), 2317; https://doi.org/10.3390/cancers14092317 - 7 May 2022
Cited by 32 | Viewed by 5666
Abstract
Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), [...] Read more.
Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), circulating freely in the blood stream or entrapped in extracellular vesicles (EVs), have been shown to have a potential diagnostic, prognostic or predictive power. In this review, recent findings are summarized, both at a preclinical and clinical level, related to miRNA applicability in the context of breast cancer. Different aspects, including clinical and technical challenges, are discussed, describing the potentialities of miRNA use in breast cancer. Even though more methodological standardized studies conducted in larger and selected patient cohorts are needed to support the effective clinical utility of miRNA as biomarkers, they could represent novel and accessible tools to be transferred into clinical practice. Full article
(This article belongs to the Special Issue microRNA and Oxidative Drugs in Cancer Therapy and Prevention)
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