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3 pages, 202 KiB

Open AccessEditorial

Nucleic Acids in Cancer Diagnosis and Therapy

by Taewan Kim

Cancers 2023, 15(7), 1938; https://doi.org/10.3390/cancers15071938 - 23 Mar 2023

Cited by 1 | Viewed by 1281

Abstract

Nucleic acids include two main classes: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) [...] Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

2 pages, 155 KiB

Open AccessEditorial

Nucleic Acids in Cancer Diagnosis and Therapy

by Taewan Kim

Cancers 2020, 12(9), 2597; https://doi.org/10.3390/cancers12092597 - 11 Sep 2020

Cited by 4 | Viewed by 1962

Abstract

Cancer research has been focused on the coding genes occupying 1–2% of the human genome [...] Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

Research

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12 pages, 944 KiB

Open AccessArticle

NOTCH1 Intracellular Domain and the Tumor Microenvironment as Prognostic Markers in HNSCC

by Benedikt Schmidl, Michael Siegl, Melanie Boxberg, Fabian Stögbauer, Daniel Jira, Christof Winter, Leonhard Stark, Anja Pickhard, Barbara Wollenberg and Markus Wirth

Cancers 2022, 14(4), 1080; https://doi.org/10.3390/cancers14041080 - 21 Feb 2022

Cited by 7 | Viewed by 2746

Abstract

(1) Background: NOTCH1 is the second most common mutated gene in whole-exome sequencing of HNSCC. The aim of this project was to gain further insight into the relevance of NOTCH1 in HNSCC, potentially establishing NOTCH1 as a prognostic marker or therapeutic target; (2) [...] Read more.

(1) Background: NOTCH1 is the second most common mutated gene in whole-exome sequencing of HNSCC. The aim of this project was to gain further insight into the relevance of NOTCH1 in HNSCC, potentially establishing NOTCH1 as a prognostic marker or therapeutic target; (2) Methods: NOTCH1 was silenced via RNA interference in six HNSCC cell lines and the impact was evaluated in migration and proliferation assays. Subsequently, the protein expression of NOTCH1 intracellular domain (NICD) and NOTCH1 mRNA expression were examined in 70 oropharyngeal squamous cell cancer tissue samples. Lastly, the NICD expression was compared with the local infiltration of lymphocytes, measured with the immunoscore; (3) Results: Knockdown of NOTCH1 decreased migration and proliferation. A high NICD expression was associated with lower OS. A high immunoscore resulted in significantly better OS. NICD expression was independent of the immunoscore and as a whole differentiated three distinct prognostic groups; (4) Conclusions: These data suggest that NOTCH1 is involved in migration and proliferation of HNSCC cell lines. In vivo, NICD expression was associated with overall survival and could, therefore, be used as a prognostic marker. NICD expression differs from NOTCH1 mRNA levels, potentially explaining the previously suggested bimodal role as an oncogene and tumor suppressor in HNSCC. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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14 pages, 3823 KiB

Open AccessArticle

Disparities in Lung Cancer: miRNA Isoform Characterization in Lung Adenocarcinoma

by Rosario Distefano, Giovanni Nigita, Patricia Le, Giulia Romano, Mario Acunzo and Patrick Nana-Sinkam

Cancers 2022, 14(3), 773; https://doi.org/10.3390/cancers14030773 - 2 Feb 2022

Cited by 5 | Viewed by 2355

Abstract

Despite the development of targeted therapeutics, immunotherapy, and strategies for early detection, lung cancer carries a high mortality. Further, significant racial disparities in outcomes exist for which the molecular drivers have yet to be fully elucidated. The growing field of Epitranscriptomics has introduced [...] Read more.

Despite the development of targeted therapeutics, immunotherapy, and strategies for early detection, lung cancer carries a high mortality. Further, significant racial disparities in outcomes exist for which the molecular drivers have yet to be fully elucidated. The growing field of Epitranscriptomics has introduced a new layer of complexity to the molecular pathogenesis of cancer. RNA modifications can occur in coding and non-coding RNAs, such as miRNAs, possibly altering their gene regulatory function. The potential role for such modifications as clinically informative biomarkers remains largely unknown. Here, we concurrently profiled canonical miRNAs, shifted isomiRs (templated and non-templated), and miRNAs with single-point modification events (RNA and DNA) in White American (W) and Black or African American (B/AA) lung adenocarcinoma (LUAD) patients. We found that while most deregulated miRNA isoforms were similar in W and B/AA LUAD tissues compared to normal adjacent tissues, there was a subgroup of isoforms with deregulation according to race. We specifically investigated an edited miRNA, miR-151a-3p with an A-to-I editing event at position 3, to determine how its altered expression may be associated with activation of divergent biological pathways between W and B/AA LUAD patients. Finally, we identified distinct race-specific miRNA isoforms that correlated with prognosis for both Ws and B/AAs. Our results suggested that concurrently profiling canonical and non-canonical miRNAs may have potential as a strategy for identifying additional distinct biological pathways and biomarkers in lung cancer. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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15 pages, 1691 KiB

Open AccessArticle

Noncoding RNAs and Deep Learning Neural Network Discriminate Multi-Cancer Types

by Anyou Wang, Rong Hai, Paul J. Rider and Qianchuan He

Cancers 2022, 14(2), 352; https://doi.org/10.3390/cancers14020352 - 12 Jan 2022

Cited by 6 | Viewed by 2438

Abstract

Detecting cancers at early stages can dramatically reduce mortality rates. Therefore, practical cancer screening at the population level is needed. To develop a comprehensive detection system to classify multiple cancer types, we integrated an artificial intelligence deep learning neural network and noncoding RNA [...] Read more.

Detecting cancers at early stages can dramatically reduce mortality rates. Therefore, practical cancer screening at the population level is needed. To develop a comprehensive detection system to classify multiple cancer types, we integrated an artificial intelligence deep learning neural network and noncoding RNA biomarkers selected from massive data. Our system can accurately detect cancer vs. healthy objects with 96.3% of AUC of ROC (Area Under Curve of a Receiver Operating Characteristic curve), and it surprisingly reaches 78.77% of AUC when validated by real-world raw data from a completely independent data set. Even validating with raw exosome data from blood, our system can reach 72% of AUC. Moreover, our system significantly outperforms conventional machine learning models, such as random forest. Intriguingly, with no more than six biomarkers, our approach can easily discriminate any individual cancer type vs. normal with 99% to 100% AUC. Furthermore, a comprehensive marker panel can simultaneously multi-classify common cancers with a stable 82.15% accuracy rate for heterogeneous cancerous tissues and conditions. This detection system provides a promising practical framework for automatic cancer screening at population level. Key points: (1) We developed a practical cancer screening system, which is simple, accurate, affordable, and easy to operate. (2) Our system binarily classify cancers vs. normal with >96% AUC. (3) In total, 26 individual cancer types can be easily detected by our system with 99 to 100% AUC. (4) The system can detect multiple cancer types simultaneously with >82% accuracy. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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21 pages, 8401 KiB

Open AccessArticle

Expression of SnoRNA U50A Is Associated with Better Prognosis and Prolonged Mitosis in Breast Cancer

by Jie-Ning Li, Ming-Yang Wang, Yi-Ting Chen, Yao-Lung Kuo and Pai-Sheng Chen

Cancers 2021, 13(24), 6304; https://doi.org/10.3390/cancers13246304 - 15 Dec 2021

Cited by 8 | Viewed by 2205

Abstract

Small nucleolar RNAs (snoRNAs) are small noncoding RNAs generally recognized as housekeeping genes. Genomic analysis has shown that snoRNA U50A (U50A) is a candidate tumor suppressor gene deleted in less than 10% of breast cancer patients. To date, the pathological roles of U50A [...] Read more.

Small nucleolar RNAs (snoRNAs) are small noncoding RNAs generally recognized as housekeeping genes. Genomic analysis has shown that snoRNA U50A (U50A) is a candidate tumor suppressor gene deleted in less than 10% of breast cancer patients. To date, the pathological roles of U50A in cancer, including its clinical significance and its regulatory impact at the molecular level, are not well-defined. Here, we quantified the copy number of U50A in human breast cancer tissues. Our results showed that the U50A expression level is correlated with better prognosis in breast cancer patients. Utilizing RNA-sequencing for transcriptomic analysis, we revealed that U50A downregulates mitosis-related genes leading to arrested cancer cell mitosis and suppressed colony-forming ability. Moreover, in support of the impacts of U50A in prolonging mitosis and inhibiting clonogenic activity, breast cancer tissues with higher U50A expression exhibit accumulated mitotic tumor cells. In conclusion, based on the evidence from U50A-downregulated mitosis-related genes, prolonged mitosis, repressed colony-forming ability, and clinical analyses, we demonstrated molecular insights into the pathological impact of snoRNA U50A in human breast cancer. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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18 pages, 2979 KiB

Open AccessArticle

miR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN

by Xiaohui Zhang, Tingyu Li, Ya-Nan Han, Minghui Ge, Pei Wang, Lina Sun, Hao Liu, Tianyu Cao, Yongzhan Nie, Daiming Fan, Hao Guo, Kaichun Wu, Xiaodi Zhao and Yuanyuan Lu

Cancers 2021, 13(22), 5710; https://doi.org/10.3390/cancers13225710 - 15 Nov 2021

Cited by 22 | Viewed by 2633

Abstract

Metastasis contributes to the poor prognosis of colorectal cancer, the causative factor of which is not fully understood. Previously, we found that miR-125b (Accession number: MIMAT0000423) contributed to cetuximab resistance in colorectal cancer (CRC). In this study, we identified a novel mechanism by [...] Read more.

Metastasis contributes to the poor prognosis of colorectal cancer, the causative factor of which is not fully understood. Previously, we found that miR-125b (Accession number: MIMAT0000423) contributed to cetuximab resistance in colorectal cancer (CRC). In this study, we identified a novel mechanism by which miR-125b enhances metastasis by targeting cystic fibrosis transmembrane conductance regulator (CFTR) and the tight junction-associated adaptor cingulin (CGN) in CRC. We found that miR-125b expression was upregulated in primary CRC tumors and metastatic sites compared with adjacent normal tissues. Overexpression of miR-125b in CRC cells enhanced migration capacity, while knockdown of miR-125b decreased migration and invasion. RNA-sequencing (RNA-seq) and dual-luciferase reporter assays identified CFTR and CGN as the target genes of miR-125b, and the inhibitory impact of CFTR and CGN on metastasis was further verified both in vitro and in vivo. Moreover, we found that miR-125b facilitated the epithelial-mesenchymal transition (EMT) process and the expression and secretion of urokinase plasminogen activator (uPA) by targeting CFTR and enhanced the Ras Homolog Family Member A (RhoA)/Rho Kinase (ROCK) pathway activity by targeting CGN. Together, these findings suggest miR-125b as a key functional molecule in CRC and a promising biomarker for the diagnosis and treatment of CRC. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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12 pages, 2857 KiB

Open AccessArticle

Tumor Suppressive Circular RNA-102450: Development of a Novel Diagnostic Procedure for Lymph Node Metastasis from Oral Cancer

by Toshiaki Ando, Atsushi Kasamatsu, Kohei Kawasaki, Kazuya Hiroshima, Reo Fukushima, Manabu Iyoda, Dai Nakashima, Yosuke Endo-Sakamoto and Katsuhiro Uzawa

Cancers 2021, 13(22), 5708; https://doi.org/10.3390/cancers13225708 - 15 Nov 2021

Cited by 6 | Viewed by 1881

Abstract

Circular RNAs (circRNAs), which form as covalently closed loop structures, have several biological functions such as regulation of cellular behavior by adsorbing microRNAs. However, there is limited information of circRNAs in oral squamous cell carcinoma (OSCC). Here, we aimed to elucidate the roles [...] Read more.

Circular RNAs (circRNAs), which form as covalently closed loop structures, have several biological functions such as regulation of cellular behavior by adsorbing microRNAs. However, there is limited information of circRNAs in oral squamous cell carcinoma (OSCC). Here, we aimed to elucidate the roles of aberrantly expressed circRNAs in OSCC. CircRNA microarray showed that circRNA-102450 was down-regulated in OSCC cells. Clinical validation of circRNA-102450 was performed using highly sensitive droplet digital PCR in preoperative liquid biopsy samples from 30 OSCC patients. Interestingly, none of 16 studied patients with high circRNA-102450 had regional lymph node metastasis (RLNM), whereas 4 of 14 studied patients (28.5%) with low expression had pathologically proven RLNM. Overexpressed circRNA-102450 significantly inhibited the tumor metastatic properties of cell proliferation, migration, and invasion. Furthermore, circRNA-102450 directly bound to, and consequently down-regulated, miR-1178 in OSCC cells. Taken together, circRNA-102450 has a tumor suppressive effect via the circRNA-102450/miR-1178 axis and may be a novel potential marker of RLNM in OSCC patients. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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12 pages, 1210 KiB

Open AccessArticle

miRNA Expression Signatures of Therapy Response in Squamous Cell Carcinomas

by János Tibor Fekete, Ágnes Welker and Balázs Győrffy

Cancers 2021, 13(1), 63; https://doi.org/10.3390/cancers13010063 - 28 Dec 2020

Cited by 11 | Viewed by 2926

Abstract

Introduction: Squamous cell carcinomas (SCC) are a major subgroup of malignant tumors with a platinum-based first-line systematic chemotherapy. miRNAs play a role in various diseases and modulate therapy response as well. The aim of this study was to identify predictive miRNAs in platinum-treated [...] Read more.

Introduction: Squamous cell carcinomas (SCC) are a major subgroup of malignant tumors with a platinum-based first-line systematic chemotherapy. miRNAs play a role in various diseases and modulate therapy response as well. The aim of this study was to identify predictive miRNAs in platinum-treated SCCs. Methods: miRNA expression data of platinum-treated head and neck (HNSC), cervical (CESC) and lung (LUSC) cancer were collected from the TCGA repositories. Treatment response was defined based on presence or absence of disease progression at 18 months. Responder and nonresponder cohorts were compared using Mann–Whitney and Receiver Operating Characteristic tests. Logistic regression was developed to establish a predictive miRNA signature. Significance was set at FDR < 5%. Results: The integrated database includes 266 SCC patient samples with platinum-based therapy and available follow-up. We uncovered 16, 103, and 9 miRNAs correlated to chemotherapy response in the CESC, HNSC, and LUSC cohorts, respectively. Eight miRNAs overlapped between the CESC and HNSC subgroups, and three miRNAs overlapped between the LUSC and HNSC subgroups. We established a logistic regression model in HNSC and CESC which included six miRNAs: hsa-miR-5586 (Exp (B): 2.94, p = 0.001), hsa-miR-632 (Exp (B): 10.75, p = 0.002), hsa-miR-2355 (Exp (B): 0.48, p = 0.004), hsa-miR-642a (Exp (B): 2.22, p = 0.01), hsa-miR-101-2 (Exp (B): 0.39, p = 0.013) and hsa-miR-6728 (Exp (B): 0.21, p = 0.016). The model using these miRNAs was able to predict chemotherapy resistance with an AUC of 0.897. Conclusions: We performed an analysis of RNA-seq data of squamous cell carcinomas samples and identified significant miRNAs correlated to the response against platinum-based therapy in cervical, head and neck, and lung tumors. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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14 pages, 2655 KiB

Open AccessArticle

DKC1 Overexpression Induces a More Aggressive Cellular Behavior and Increases Intrinsic Ribosomal Activity in Immortalized Mammary Gland Cells

by Ania Naila Guerrieri, Federico Zacchini, Carmine Onofrillo, Sara Di Viggiano, Marianna Penzo, Alessio Ansuini, Ilaria Gandin, Yuko Nobe, Masato Taoka, Toshiaki Isobe, Davide Treré and Lorenzo Montanaro

Cancers 2020, 12(12), 3512; https://doi.org/10.3390/cancers12123512 - 25 Nov 2020

Cited by 17 | Viewed by 3765

Abstract

Dyskerin is a nucleolar protein involved in the small nucleolar RNA (snoRNA)-guided pseudouridylation of specific uridines on ribosomal RNA (rRNA), and in the stabilization of the telomerase RNA component (hTR). Loss of function mutations in DKC1 causes X-linked dyskeratosis congenita, which is characterized [...] Read more.

Dyskerin is a nucleolar protein involved in the small nucleolar RNA (snoRNA)-guided pseudouridylation of specific uridines on ribosomal RNA (rRNA), and in the stabilization of the telomerase RNA component (hTR). Loss of function mutations in DKC1 causes X-linked dyskeratosis congenita, which is characterized by a failure of proliferating tissues and increased susceptibility to cancer. However, several tumors show dyskerin overexpression. We observed that patients with primary breast cancers with high dyskerin levels are more frequently characterized by shorter survival rates and positive lymph node status than those with tumors with a lower dyskerin expression. To functionally characterize the effects of high dyskerin expression, we generated stably overexpressing DKC1 models finding that increased dyskerin levels conferred a more aggressive cellular phenotype in untransformed immortalized MCF10A cells. Contextually, DKC1 overexpression led to an upregulation of some snoRNAs, including SNORA67 and a significantly increased U1445 modification on 18S rRNA, the known target of SNORA67. Lastly, we found that dyskerin overexpression strongly enhanced the synthetic activity of ribosomes increasing translational efficiency in MCF10A. Altogether, our results indicate that dyskerin may sustain the neoplastic phenotype from an early stage in breast cancer endowing ribosomes with an augmented translation efficiency. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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Review

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16 pages, 1010 KiB

Open AccessReview

Albumin Nanostructures for Nucleic Acid Delivery in Cancer: Current Trend, Emerging Issues, and Possible Solutions

by Rama Prajapati and Álvaro Somoza

Cancers 2021, 13(14), 3454; https://doi.org/10.3390/cancers13143454 - 9 Jul 2021

Cited by 24 | Viewed by 4245

Abstract

Cancer is one of the major health problems worldwide, and hence, suitable therapies with enhanced efficacy and reduced side effects are desired. Gene therapy, involving plasmids, small interfering RNAs, and antisense oligonucleotides have been showing promising potential in cancer therapy. In recent years, [...] Read more.

Cancer is one of the major health problems worldwide, and hence, suitable therapies with enhanced efficacy and reduced side effects are desired. Gene therapy, involving plasmids, small interfering RNAs, and antisense oligonucleotides have been showing promising potential in cancer therapy. In recent years, the preparation of various carriers for nucleic acid delivery to the tumor sites is gaining attention since intracellular and extracellular barriers impart major challenges in the delivery of naked nucleic acids. Albumin is a versatile protein being used widely for developing carriers for nucleic acids. It provides biocompatibility, tumor specificity, the possibility for surface modification, and reduces toxicity. In this review, the advantages of using nucleic acids in cancer therapy and the challenges associated with their delivery are presented. The focus of this article is on the different types of albumin nanocarriers, such as nanoparticles, polyplexes, and nanoconjugates, employed to overcome the limitations of the direct use of nucleic acids in vivo. This review also highlights various approaches for the modification of the surface of albumin to enhance its transfection efficiency and targeted delivery in the tumor sites. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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19 pages, 1663 KiB

Open AccessReview

Detecting and Characterizing A-To-I microRNA Editing in Cancer

by Gioacchino P. Marceca, Luisa Tomasello, Rosario Distefano, Mario Acunzo, Carlo M. Croce and Giovanni Nigita

Cancers 2021, 13(7), 1699; https://doi.org/10.3390/cancers13071699 - 3 Apr 2021

Cited by 21 | Viewed by 3830

Abstract

Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either [...] Read more.

Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. The employment of powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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25 pages, 1695 KiB

Open AccessReview

Non-Coding RNAs in Cancer Diagnosis and Therapy: Focus on Lung Cancer

by Patricia Le, Giulia Romano, Patrick Nana-Sinkam and Mario Acunzo

Cancers 2021, 13(6), 1372; https://doi.org/10.3390/cancers13061372 - 18 Mar 2021

Cited by 47 | Viewed by 3852

Abstract

Over the last several decades, clinical evaluation and treatment of lung cancers have largely improved with the classification of genetic drivers of the disease, such as EGFR, ALK, and ROS1. There are numerous regulatory factors that exert cellular control over key oncogenic pathways [...] Read more.

Over the last several decades, clinical evaluation and treatment of lung cancers have largely improved with the classification of genetic drivers of the disease, such as EGFR, ALK, and ROS1. There are numerous regulatory factors that exert cellular control over key oncogenic pathways involved in lung cancers. In particular, non-coding RNAs (ncRNAs) have a diversity of regulatory roles in lung cancers such that they have been shown to be involved in inducing proliferation, suppressing apoptotic pathways, increasing metastatic potential of cancer cells, and acquiring drug resistance. The dysregulation of various ncRNAs in human cancers has prompted preclinical studies examining the therapeutic potential of restoring and/or inhibiting these ncRNAs. Furthermore, ncRNAs demonstrate tissue-specific expression in addition to high stability within biological fluids. This makes them excellent candidates as cancer biomarkers. This review aims to discuss the relevance of ncRNAs in cancer pathology, diagnosis, and therapy, with a focus on lung cancer. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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22 pages, 796 KiB

Open AccessReview

MicroRNA in Papillary Thyroid Carcinoma: A Systematic Review from 2018 to June 2020

by Liviu Hitu, Katalin Gabora, Eduard-Alexandru Bonci, Andra Piciu, Adriana-Cezara Hitu, Paul-Andrei Ștefan and Doina Piciu

Cancers 2020, 12(11), 3118; https://doi.org/10.3390/cancers12113118 - 25 Oct 2020

Cited by 18 | Viewed by 2885

Abstract

The involvement of micro-ribonucleic acid (microRNAs) in metabolic pathways such as regulation, signal transduction, cell maintenance, and differentiation make them possible biomarkers and therapeutic targets. The purpose of this review is to summarize the information published in the last two and a half [...] Read more.

The involvement of micro-ribonucleic acid (microRNAs) in metabolic pathways such as regulation, signal transduction, cell maintenance, and differentiation make them possible biomarkers and therapeutic targets. The purpose of this review is to summarize the information published in the last two and a half years about the involvement of microRNAs in papillary thyroid carcinoma (PTC). Another goal is to understand the perspective offered by the new findings. Main microRNA features such as origin, regulation, targeted genes, and metabolic pathways will be presented in this paper. We interrogated the PubMed database using several keywords: “microRNA” + “thyroid” + “papillary” + “carcinoma”. After applying search filters and inclusion criteria, a selection of 137 articles published between January 2018–June 2020 was made. Data regarding microRNA, metabolic pathways, gene/protein, and study utility were selected and included in the table and later discussed regarding the matter at hand. We found that most microRNAs regularly expressed in the normal thyroid gland are downregulated in PTC, indicating an important tumor-suppressor action by those microRNAs. Moreover, we showed that one gene can be targeted by several microRNAs and have nominally described these interactions. We have revealed which microRNAs can target several genes at once. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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33 pages, 1830 KiB

Open AccessReview

RNA-Binding Proteins in Cancer: Functional and Therapeutic Perspectives

by Donghee Kang, Yerim Lee and Jae-Seon Lee

Cancers 2020, 12(9), 2699; https://doi.org/10.3390/cancers12092699 - 21 Sep 2020

Cited by 92 | Viewed by 9622

Abstract

RNA-binding proteins (RBPs) crucially regulate gene expression through post-transcriptional regulation, such as by modulating microRNA (miRNA) processing and the alternative splicing, alternative polyadenylation, subcellular localization, stability, and translation of RNAs. More than 1500 RBPs have been identified to date, and many of them [...] Read more.

RNA-binding proteins (RBPs) crucially regulate gene expression through post-transcriptional regulation, such as by modulating microRNA (miRNA) processing and the alternative splicing, alternative polyadenylation, subcellular localization, stability, and translation of RNAs. More than 1500 RBPs have been identified to date, and many of them are known to be deregulated in cancer. Alterations in the expression and localization of RBPs can influence the expression levels of oncogenes, tumor-suppressor genes, and genome stability-related genes. RBP-mediated gene regulation can lead to diverse cancer-related cellular phenotypes, such as proliferation, apoptosis, angiogenesis, senescence, and epithelial-mesenchymal transition (EMT)/invasion/metastasis. This regulation can also be associated with cancer prognosis. Thus, RBPs can be potential targets for the development of therapeutics for the cancer treatment. In this review, we describe the molecular functions of RBPs, their roles in cancer-related cellular phenotypes, and various approaches that may be used to target RBPs for cancer treatment. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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23 pages, 1433 KiB

Open AccessReview

Coding of Glioblastoma Progression and Therapy Resistance through Long Noncoding RNAs

by Alja Zottel, Neja Šamec, Alja Videtič Paska and Ivana Jovčevska

Cancers 2020, 12(7), 1842; https://doi.org/10.3390/cancers12071842 - 8 Jul 2020

Cited by 30 | Viewed by 4112

Abstract

Glioblastoma is the most aggressive and lethal primary brain malignancy, with an average patient survival from diagnosis of 14 months. Glioblastoma also usually progresses as a more invasive phenotype after initial treatment. A major step forward in our understanding of the nature of [...] Read more.

Glioblastoma is the most aggressive and lethal primary brain malignancy, with an average patient survival from diagnosis of 14 months. Glioblastoma also usually progresses as a more invasive phenotype after initial treatment. A major step forward in our understanding of the nature of glioblastoma was achieved with large-scale expression analysis. However, due to genomic complexity and heterogeneity, transcriptomics alone is not enough to define the glioblastoma “fingerprint”, so epigenetic mechanisms are being examined, including the noncoding genome. On the basis of their tissue specificity, long noncoding RNAs (lncRNAs) are being explored as new diagnostic and therapeutic targets. In addition, growing evidence indicates that lncRNAs have various roles in resistance to glioblastoma therapies (e.g., MALAT1, H19) and in glioblastoma progression (e.g., CRNDE, HOTAIRM1, ASLNC22381, ASLNC20819). Investigations have also focused on the prognostic value of lncRNAs, as well as the definition of the molecular signatures of glioma, to provide more precise tumor classification. This review discusses the potential that lncRNAs hold for the development of novel diagnostic and, hopefully, therapeutic targets that can contribute to prolonged survival and improved quality of life for patients with glioblastoma. Full article

(This article belongs to the Special Issue Nucleic Acids in Cancer Diagnosis and Therapy)

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