During the last decade, high-throughput sequencing efforts in the fields of transcriptomics and epigenomics have shed light on the noncoding part of the transcriptome and its potential role in human disease. Regulatory noncoding RNAs are broadly divided into short and long noncoding transcripts. The latter, also known as lncRNAs, are defined as transcripts longer than 200 nucleotides with low or no protein-coding potential. LncRNAs form a diverse group of transcripts that regulate vital cellular functions through interactions with proteins, chromatin, and even RNA itself. Notably, an important regulatory aspect of these RNA species is their association with the epigenetic machinery and the recruitment of its regulatory apparatus to specific loci, resulting in DNA methylation and/or post-translational modifications of histones. Such epigenetic modifications play a pivotal role in maintaining the active or inactive transcriptional state of chromatin and are crucial regulators of normal cellular development and tissue-specific gene expression. Evidently, aberrant expression of lncRNAs that interact with epigenetic modifiers can cause severe epigenetic disruption and is thus is closely associated with altered gene function, cellular dysregulation, and malignant transformation. Here, we survey the latest breakthroughs concerning the role of lncRNAs interacting with the epigenetic machinery in various forms of cancer.

The cancer genome is characterized by extensive variability, in the form of Single Nucleotide Polymorphisms (SNPs) or structural variations such as Copy Number Alterations (CNAs) across wider genomic areas. At the molecular level, most SNPs and/or CNAs reside in non-coding sequences, ultimately affecting the regulation of oncogenes and/or tumor-suppressors in a cancer-specific manner. Notably, inherited non-coding variants can predispose for cancer decades prior to disease onset. Furthermore, accumulation of additional non-coding driver mutations during progression of the disease, gives rise to genomic instability, acting as the driving force of neoplastic development and malignant evolution. Therefore, detection and characterization of such mutations can improve risk assessment for healthy carriers and expand the diagnostic and therapeutic toolbox for the patient. This review focuses on functional variants that reside in transcribed or not transcribed non-coding regions of the cancer genome and presents a collection of appropriate state-of-the-art methodologies to study them.

Background: Marine seaweeds are considered as a rich source of health-promoting compounds by the food and pharmaceutical industry. Hypnea musciformis is a marine red macroalga (seaweed) that is widely distributed throughout the world, including the Mediterranean Sea. It is known to contain various bioactive compounds, including sulfated polysaccharides, flavonoids, and phlorotannins. Recent studies have investigated the potential anticancer effects of extracts from H. musciformis demonstrating their cytotoxic effects on various cancer cell lines. The anticancer effects of these extracts are thought to be due to the presence of bioactive compounds, particularly sulfated polysaccharides, which have been shown to have anticancer and immunomodulatory effects. However, further studies are needed to fully understand the molecular mechanisms that underlie their anticancer effects and to determine their potential as therapeutic agents for cancer treatment. Methods: H. musciformis was collected from the Aegean Sea (Greece) and used for extract preparation. Transcriptome and proteome analysis was performed in liver and colon cancer human cell lines following treatment with H. musciformis seaweed extracts to characterize its anticancer effect in detail at the molecular level and to link transcriptome and proteome responses to the observed phenotypes in cancer cells. Results: We have identified that treatment with the seaweed extract triggers a p53-mediated response at the transcriptional and protein level in liver cancer cells, in contrast to colon cancer cells in which the effects are more associated with metabolic changes. Furthermore, we show that in treated HepG2 liver cancer cells, p53 interacts with the chromatin of several target genes and facilitates their upregulation possibly through the recruitment of the p300 co-activator. Conclusions: Overall, the available evidence suggests that extracts from H. musciformis have the potential to serve as a source of anticancer agents in liver cancer cells mainly through activation of a p53-mediated anti-tumor response that is linked to inhibition of cellular proliferation and induction of cell death.

The genetic diversity among the main local landraces and commercial cultivars of P. vulgaris L. cultivated in Greece, was estimated by studying the morphological, agronomical and physicochemical traits along with molecular data analysis using random amplified polymorphic DNA (RAPD markers). Cluster analysis was conducted on similarity estimates using the UPGMA algorithm. Application of cluster analysis resulted in a dendrogram representing the genetic relationship among landraces and main bean cultivars grown in Greece. A wide genetic variation was observed among collected local bean landraces in morphological characteristics such as seed color, seed size and growth habit. According to agronomic performance, significant differences were found in number and weight of pods per plant. Variation in protein and fat content among landraces and commercial cultivars was also detected. Moreover, in some landraces like Kastoria and Byzitsa M/M extremely high values for protein content (28.6% and 27.0% respectively) were recorded. Such values were greater than the average protein content previously recorded for other cultivars of this species. Genetic similarity estimated from molecular analysis with RAPDs, seemed not to be related with the seed morphological characteristics and agronomic performance. Only qualitative parameters like growth habit and occasionally geographical origin of landraces were positively correlated with the molecular classification. Local bean landraces were classified in three subgroups whereas the commercial cultivars formed another separate group underlining the narrow genetic base of cultivars.

Worldwide, Cucumber mosaic virus (CMV) is the causal agent of many economically important diseases. Based on immunological or molecular analysis, three distinct subgroups of CMV isolates can be identified (IA, IB, and II). In addition, some CMV isolates are associated with satellite RNAs (satRNAs), a type of noncoding transcript that may alter the symptoms of CMV infections. This study presents an analysis of CMV isolates occurring in legumes in Greece in respect to their genetic diversity, and the presence and diversity of their satRNA. Phylogenetic analysis of the CMV coat protein sequence of 18 legume and 5 tomato CMV isolates collected throughout Greece classified them within subgroups IA and IB, with a limited genetic diversity. The CMV satRNAs found in nine field legumes exhibiting mild symptoms and in one tomato with a necrotic syndrome contained a functional necrogenic motif; therefore, they were grouped within the necrogenic group of CMV-satRNAs. The necrotic phenotype was expressed in all legume CMV isolates containing necrogenic satRNAs when mechanically inoculated onto tomato plants. To our knowledge, this is the first observation that legumes host necrogenic CMV-satRNAs. The possible role of legumes in the epidemiology of CMV and necrogenic satRNA complex is discussed.

During the metagenomics era, high-throughput sequencing efforts both in mice and humans indicate that non-coding RNAs (ncRNAs) constitute a significant fraction of the transcribed genome. During the past decades, the regulatory role of these non-coding transcripts along with their interactions with other molecules have been extensively characterized. However, the study of long non-coding RNAs (lncRNAs), an ncRNA regulatory class with transcript lengths that exceed 200 nucleotides, revealed that certain non-coding transcripts are transcriptional “by-products”, while their loci exert their downstream regulatory functions through RNA-independent mechanisms. Such mechanisms include, but are not limited to, chromatin interactions and complex promoter-enhancer competition schemes that involve the underlying ncRNA locus with or without its nascent transcription, mediating significant or even exclusive roles in the regulation of downstream target genes in mammals. Interestingly, such RNA-independent mechanisms often drive pathological manifestations, including oncogenesis. In this review, we summarize selective examples of lncRNAs that regulate target genes independently of their produced transcripts.