Beyond MicroRNAs: Emerging Role of Other Non-Coding RNAs in HPV-Driven Cancers

Persistent infection with high-risk Human Papilloma Virus (HPV) leads to the development of several tumors, including cervical, oropharyngeal, and anogenital squamous cell carcinoma. In the last years, the use of high-throughput sequencing technologies has revealed a number of non-coding RNA (ncRNAs), distinct from micro RNAs (miRNAs), that are deregulated in HPV-driven cancers, thus suggesting that HPV infection may affect their expression. However, since the knowledge of ncRNAs is still limited, a better understanding of ncRNAs biology, biogenesis, and function may be challenging for improving the diagnosis of HPV infection or progression, and for monitoring the response to therapy of patients affected by HPV-driven tumors. In addition, to establish a ncRNAs expression profile may be instrumental for developing more effective therapeutic strategies for the treatment of HPV-associated lesions and cancers. Therefore, this review will address novel classes of ncRNAs that have recently started to draw increasing attention in HPV-driven tumors, with a particular focus on ncRNAs that have been identified as a direct target of HPV oncoproteins.

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Profiling DNA Methylation Based on Next-Generation Sequencing Approaches: New Insights and Clinical Applications

Genes ◽

10.3390/genes9090429 ◽

2018 ◽

Vol 9 (9) ◽

pp. 429 ◽

Cited By ~ 38

Author(s):

Daniela Barros-Silva ◽

C. Marques ◽

Rui Henrique ◽

Carmen Jerónimo

Keyword(s):

Dna Methylation ◽

Next Generation Sequencing ◽

High Throughput Sequencing ◽

Epigenetic Modification ◽

Response To Therapy ◽

Next Generation ◽

Sequencing Technologies ◽

Prognosis And Prediction ◽

Novel Biomarkers ◽

Generation Sequencing

DNA methylation is an epigenetic modification that plays a pivotal role in regulating gene expression and, consequently, influences a wide variety of biological processes and diseases. The advances in next-generation sequencing technologies allow for genome-wide profiling of methyl marks both at a single-nucleotide and at a single-cell resolution. These profiling approaches vary in many aspects, such as DNA input, resolution, coverage, and bioinformatics analysis. Thus, the selection of the most feasible method according with the project’s purpose requires in-depth knowledge of those techniques. Currently, high-throughput sequencing techniques are intensively used in epigenomics profiling, which ultimately aims to find novel biomarkers for detection, diagnosis prognosis, and prediction of response to therapy, as well as to discover new targets for personalized treatments. Here, we present, in brief, a portrayal of next-generation sequencing methodologies’ evolution for profiling DNA methylation, highlighting its potential for translational medicine and presenting significant findings in several diseases.

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Origins and Function of VL30 lncRNA Packaging in Small Extracellular Vesicles: Implications for Cellular Physiology and Pathology

Biomedicines ◽

10.3390/biomedicines9111742 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1742

Author(s):

Stefania Mantziou ◽

Georgios S. Markopoulos

Keyword(s):

Extracellular Vesicles ◽

Active Regions ◽

Regulatory Elements ◽

Binding Motif ◽

Regulatory Sequences ◽

Chromosomal Distribution ◽

Non Coding Rna ◽

Rna Biology ◽

And Function

Long non-coding RNAs (lncRNAs) have emerged during the post-genomic era as significant epigenetic regulators. Viral-like 30 elements (VL30s) are a family of mouse retrotransposons that are transcribed into functional lncRNAs. Recent data suggest that VL30 RNAs are efficiently packaged in small extracellular vesicles (SEVs) through an SEV enrichment sequence. We analysed VL30 elements for the presence of the distinct 26 nt SEV enrichment motif and found that SEV enrichment is an inherent hallmark of the VL30 family, contained in 36 full-length elements, with a widespread chromosomal distribution. Among them, 25 elements represent active, present-day integrations and contain an abundance of regulatory sequences. Phylogenetic analysis revealed a recent spread of SEV-VL30s from 4.4 million years ago till today. Importantly, 39 elements contain an SFPQ-binding motif, associated with the transcriptional induction of oncogenes. Most SEV-VL30s reside in transcriptionally active regions, as characterised by their distribution adjacent to candidate cis-regulatory elements (cCREs). Network analysis of SEV-VL30-associated genes suggests a distinct transcriptional footprint associated with embryonal abnormalities and neoplasia. Given the established role of VL30s in oncogenesis, we conclude that their potential to spread through SEVs represents a novel mechanism for non-coding RNA biology with numerous implications for cellular homeostasis and disease.

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The Role of Circular RNAs in Keratinocyte Carcinomas

Cancers ◽

10.3390/cancers13164240 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4240

Author(s):

Thomas Meyer ◽

Michael Sand ◽

Lutz Schmitz ◽

Eggert Stockfleth

Keyword(s):

Epithelial To Mesenchymal Transition ◽

Circular Rnas ◽

Mesenchymal Transition ◽

Rna Molecules ◽

Factors Associated ◽

New Therapeutic Approaches ◽

Non Coding Rna ◽

Micro Rnas ◽

Pubmed Search

Keratinocyte carcinomas (KC) include basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC) and represents the most common cancer in Europe and North America. Both entities are characterized by a very high mutational burden, mainly UV signature mutations. Predominately mutated genes in BCC belong to the sonic hedgehog pathway, whereas, in cSCC, TP53, CDKN2A, NOTCH1/2 and others are most frequently mutated. In addition, the dysregulation of factors associated with epithelial to mesenchymal transition (EMT) was shown in invasive cSCC. The expression of factors associated with tumorigenesis can be controlled in several ways and include non-coding RNA molecules, such as micro RNAs (miRNA) long noncoding RNAs (lncRNA) and circular RNAs (circRNA). To update findings on circRNA in KC, we reviewed 13 papers published since 2016, identified in a PubMed search. In both BCC and cSCC, numerous circRNAs were identified that were differently expressed compared to healthy skin. Some of them were shown to target miRNAs that are also dysregulated in KC. Moreover, some studies confirmed the biological functions of individual circRNAs involved in cancer development. Thus, circRNAs may be used as biomarkers of disease and disease progression and represent potential targets of new therapeutic approaches for KC.

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Splicing dysregulation as a driver of breast cancer

Endocrine Related Cancer ◽

10.1530/erc-18-0068 ◽

2018 ◽

Vol 25 (9) ◽

pp. R467-R478 ◽

Cited By ~ 8

Author(s):

Abigail Read ◽

Rachael Natrajan

Keyword(s):

Breast Cancer ◽

High Throughput Sequencing ◽

Predictive Biomarkers ◽

Therapy Resistance ◽

Complete Understanding ◽

Molecular Abnormalities ◽

Sequencing Technologies ◽

Large Repertoire ◽

Positive Breast Cancer

Breast cancer is known to be a heterogeneous disease driven by a large repertoire of molecular abnormalities, which contribute to its diverse clinical behaviour. Despite the success of targeted therapy approaches for breast cancer patient management, there is still a lack of the molecular understanding of aggressive forms of the disease and clinical management of these patients remains difficult. The advent of high-throughput sequencing technologies has paved the way for a more complete understanding of the molecular make-up of the breast cancer genome. As such, it is becoming apparent that disruption of canonical splicing within breast cancer governs its clinical progression. In this review, we discuss the role of dysregulation of spliceosomal component genes and associated factors in the progression of breast cancer, their role in therapy resistance and the use of quantitative isoform expression as potential prognostic and predictive biomarkers with a particular focus on oestrogen receptor-positive breast cancer.

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Non-coding RNA bioinformatics platform for full backing of the high-throughput sequencing experiments generated by next-generation sequencing technologies

EMBnet journal ◽

10.14806/ej.18.a.461 ◽

2012 ◽

Vol 18 (A) ◽

pp. 132

Author(s):

F Licciulli ◽

A Consiglio ◽

G De Caro ◽

A Gisel ◽

G Grillo ◽

...

Keyword(s):

Next Generation Sequencing ◽

High Throughput ◽

High Throughput Sequencing ◽

Next Generation ◽

Sequencing Technologies ◽

Non Coding Rna ◽

Generation Sequencing

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The role of micro-RNAs in the female reproductive tract

Reproduction ◽

10.1530/rep-11-0240 ◽

2012 ◽

Vol 143 (5) ◽

pp. 559-576 ◽

Cited By ~ 47

Author(s):

Warren B Nothnick

Keyword(s):

Posttranslational Modifications ◽

Reproductive Tract ◽

Current Knowledge ◽

Female Reproductive Tract ◽

Micro Rna ◽

Proper Function ◽

Posttranscriptional Gene Regulation ◽

Micro Rnas ◽

And Function

Proper development and function of the female reproductive tract are essential for successful reproduction. Regulation of the differentiated functions of the organs that make up the female reproductive tract is well established to occur at multiple levels including transcription, translation, and posttranslational modifications. Micro-RNA (miRNA)-mediated posttranscriptional gene regulation has emerged as a fundamental mechanism controlling normal tissue development and function. Emerging evidence indicates that miRNAs are expressed within the organs of the female reproductive tract where they function to regulate cellular pathways necessary for proper function of these organs. In this review, the functional significance of miRNAs in the development and function of the organs of the female reproductive tract is discussed. Initial discussion focuses on the role of miRNAs in the development of the organs of the female reproductive tract highlighting recent studies that clearly demonstrate that mice with disrupted Dicer1 expression are sterile, fail to develop uterine glands, and have muted estrogen responsiveness. Next, emphasis moves to discussion on our current knowledge on the characterization of miRNA expression in each of the organs of the female reproductive tract. When possible, information is presented and discussed with respect to regulation, function, and/or functional targets of these miRNA within each specific organ of the female reproductive tract.

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Bacterial Diversity and Community in Regional Water Microbiota between Different Towns in World’s Longevity Township Jiaoling, China

Diversity ◽

10.3390/d13080361 ◽

2021 ◽

Vol 13 (8) ◽

pp. 361

Author(s):

Lei Wu ◽

Xinqiang Xie ◽

Jumei Zhang ◽

Yu Ding ◽

Qingping Wu

Keyword(s):

16S Rrna ◽

High Throughput Sequencing ◽

The Other ◽

Rrna Gene ◽

Metabolic Characteristics ◽

Kegg Pathways ◽

Healthy Longevity ◽

And Function ◽

Regional Water

Healthy longevity is associated with many factors, however, the potential correlation between longevity and microbiota remains elusive. To address this, we explored environmental microbiota from one of the world’s longevity townships in China. We used 16S rRNA gene high-throughput sequencing to analyze the composition and function of water microbiota. The composition and diversity of water microbiota significantly differed between the towns. Lactobacillus, Streptococcus, Bacteroides, Faecalibacterium, and Stenotrophomonas were only dominant in Xinpu, a town with an exceptionally high centenarian population. Several biomarkers were identified, including Flavobacterium, Acinetobacter, Paracoccus, Lactobacillales, Psychrobacter, Bacteroides, Ruminococcaceae, and Faecalibacterium, and these shown to be responsible for the significant differences between towns. The main species contributing to the differences between towns were Cyanobacteria, Cupriavidus and Ralstonia. Based on KEGG pathways showed that the predicted metabolic characteristics of the water microbiota in Xinpu towns were significantly different to those of the other towns. The results revealed significant differences in the composition and diversity of water microbiota in the longevity township. These findings provide a foundation for further research on the role of water microbiota in healthy longevity.

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Composition and Function of Chicken Gut Microbiota

Animals ◽

10.3390/ani10010103 ◽

2020 ◽

Vol 10 (1) ◽

pp. 103 ◽

Cited By ~ 11

Author(s):

Ivan Rychlik

Keyword(s):

Gut Microbiota ◽

Current Knowledge ◽

Rapid Development ◽

Specific Model ◽

Sequencing Technologies ◽

Chicken Gut Microbiota ◽

And Function ◽

Experimental Group ◽

Intended Use

Studies analyzing the composition of gut microbiota are quite common at present, mainly due to the rapid development of DNA sequencing technologies within the last decade. This is valid also for chickens and their gut microbiota. However, chickens represent a specific model for host–microbiota interactions since contact between parents and offspring has been completely interrupted in domesticated chickens. Nearly all studies describe microbiota of chicks from hatcheries and these chickens are considered as references and controls. In reality, such chickens represent an extreme experimental group since control chicks should be, by nature, hatched in nests in contact with the parent hen. Not properly realising this fact and utilising only 16S rRNA sequencing results means that many conclusions are of questionable biological relevance. The specifics of chicken-related gut microbiota are therefore stressed in this review together with current knowledge of the biological role of selected microbiota members. These microbiota members are then evaluated for their intended use as a form of next-generation probiotics.

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Harnessing the gut microbiota to promote metabolic health

Nutrition Reviews ◽

10.1093/nutrit/nuaa076 ◽

2020 ◽

Vol 78 (Supplement_3) ◽

pp. 75-78

Author(s):

Niv Zmora

Keyword(s):

Gut Microbiota ◽

Structure And Function ◽

Metabolic Phenotype ◽

Metabolic Responses ◽

Neoplastic Disease ◽

Compelling Evidence ◽

Sequencing Technologies ◽

And Function ◽

Generation Sequencing

Abstract Precision medicine has become the mainstay of modern therapeutics, especially for neoplastic disease, but this paradigm does not commonly prevail in dietary planning. Compelling evidence suggests that individual features, including the structure and function of the gut microbiota, contribute to harvesting and metabolizing energy from food, and thereby modulate the host metabolic phenotype and glucose homeostasis. Here, the concept of precision to dietary planning is highlighted by demonstrating the role of the microbiota in glucose intolerance in response to noncaloric artificial sweeteners, and by linking the microbiota and other host features to postprandial increases in blood glucose. These findings highlight the heterogeneity that exists among humans, which translates into divergent metabolic responses to similar food and warrants the adoption of next-generation sequencing technologies and advanced bioinformatics to revolutionize nutrition studies, laying the groundwork for an individually focused tailor-made practice.

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Assessment of Bioleaching Microbial Community Structure and Function Based on Next-Generation Sequencing Technologies

Minerals ◽

10.3390/min8120596 ◽

2018 ◽

Vol 8 (12) ◽

pp. 596 ◽

Cited By ~ 1

Author(s):

Shuang Zhou ◽

Min Gan ◽

Jianyu Zhu ◽

Xinxing Liu ◽

Guanzhou Qiu

Keyword(s):

Community Structure ◽

Next Generation Sequencing ◽

Microbial Ecology ◽

High Throughput ◽

High Throughput Sequencing ◽

Structure And Function ◽

Next Generation ◽

Sequencing Technologies ◽

And Function ◽

Generation Sequencing

It is widely known that bioleaching microorganisms have to cope with the complex extreme environment in which microbial ecology relating to community structure and function varies across environmental types. However, analyses of microbial ecology of bioleaching bacteria is still a challenge. To address this challenge, numerous technologies have been developed. In recent years, high-throughput sequencing technologies enabling comprehensive sequencing analysis of cellular RNA and DNA within the reach of most laboratories have been added to the toolbox of microbial ecology. The next-generation sequencing technology allowing processing DNA sequences can produce available draft genomic sequences of more bioleaching bacteria, which provides the opportunity to predict models of genetic and metabolic potential of bioleaching bacteria and ultimately deepens our understanding of bioleaching microorganism. High-throughput sequencing that focuses on targeted phylogenetic marker 16S rRNA has been effectively applied to characterize the community diversity in an ore leaching environment. RNA-seq, another application of high-throughput sequencing to profile RNA, can be for both mapping and quantifying transcriptome and has demonstrated a high efficiency in quantifying the changing expression level of each transcript under different conditions. It has been demonstrated as a powerful tool for dissecting the relationship between genotype and phenotype, leading to interpreting functional elements of the genome and revealing molecular mechanisms of adaption. This review aims to describe the high-throughput sequencing approach for bioleaching environmental microorganisms, particularly focusing on its application associated with challenges.

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