Classes Of ncRNAs Research Articles

Delineating Characteristic Sequence and Structural Features of Precursor and Mature Piwi-interacting RNAs of Epithelial Ovarian Cancer

Background: Piwi-interacting RNAs (piRNAs) are an amazing class of small noncoding RNAs (sncRNAs) known for its promising role in germline and somatic cells. Myriad functional studies have been performed to unveil the true potential of this class of ncRNAs; however, global features encoded in their sequence and structure have not been explored. Objectives: We aim to identify the sequence and structural level characteristic features of piRNAs of normal ovary (NO), and two subtypes of epithelial ovarian cancer (EOCa)- endometrioid (ENOCa), and serous ovarian cancer (SOCa) that we had reported earlier and their precursors. Methods: We have performed sequence analysis of mature piRNAs and their upstream/downstream regions as well as structural analysis of precursor piRNAs (pre-piRNAs) by examining their minimal folding energy (MFE), adjusted minimal folding energy (AMFE) and minimal folding energy index (MFEI) etc using in silico approaches. Results: We observed enrichment of U at first position and G at several other positions of mature piRNAs, which might be associated with the processing of mature piRNAs similar to what is seen in the case of miRNAs and strong target binding, respectively. In addition, we found the richness of AU in and around 20 nts upstream and downstream of precursor piRNAs (pre-piRNAs). This characteristic feature of pre-piRNAs possibly contributes to lower MFE compared to random sequences and make its secondary structure less stable which decides biogenesis of piRNAs. We also noticed that MFE, AMFE and MFEI of pre-piRNAs are comparatively less than pre-miRNAs of metazoans, plants and viruses reported in other studies, which clearly discriminate pre-piRNAs from other RNA sequences including pre-miRNAs of other organisms. Conclusion: In summary, the present study reveals key characteristic features encoded within and around mature piRNAs as well as pre-piRNAs of NO and EOCa samples that distinguish piRNAs from miRNAs and other random RNA sequences. These findings might act as a cornerstone for better understanding of biogenesis and function of piRNAs as well as will aid in easier identification of new piRNAs from unknown stretch of sequences using the characteristic features.

LncRNA HOTAIR: A Potential Prognostic Factor and Therapeutic Target in Human Cancers.

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of gene expression and physiological processes. LncRNAs are a class of ncRNAs of 200 nucleotides in length. HOX transcript antisense RNA (HOTAIR), a trans-acting lncRNA with regulatory function on transcription, can repress gene expression by recruiting chromatin modifiers. HOTAIR is an oncogenic lncRNA, and numerous studies have determined that HOTAIR is highly upregulated in a wide variety of human cancers. In this review, we briefly summarize the impact of lncRNA HOTAIR expression and functions on different human solid tumors, and emphasize the potential of HOTAIR on tumor prognosis and therapy. Here, we review the recent studies that highlight the prognostic potential of HOTAIR in drug resistance and survival, and the progress of therapies developed to target HOTAIR to date. Furthermore, targeting HOTAIR results in the suppression of HOTAIR expression or function. Thus, HOTAIR knockdown exhibits great therapeutic potential in various cancers, indicating that targeting lncRNA HOTAIR may serve as a promising strategy for cancer therapy. We also propose that preclinical studies involving HOTAIR are required to provide a better understanding of the exact molecular mechanisms underlying the dysregulation of its expression and function in different human cancers and to explore effective methods of targeting HOTAIR and engineering efficient and targeted drug delivery methods in vivo.

LncRNAs as putative biomarkers and therapeutic targets for Parkinson's disease.

Parkinson's disease (PD) is known as one of the most common degenerative disorders related to the damage of the central nervous system (CNS). This brain disorder is also characterized by the formation of Lewy bodies in the cytoplasm of the dopaminergic neurons in the substantia nigra pars compacta (SNc), which consequently leads to motor and non-motor symptoms. With regard to the growing trend in the number of cases with PD and its effects on individuals, families, and communities, immediate treatments together with diagnostic methods are required. In this respect, long non-coding ribonucleic acids (lncRNAs) represent a large class of ncRNAs with more than 200 nucleotides in length, playing key roles in some important processes including gene expression, cell differentiation, genomic imprinting, apoptosis, and cell cycle. They are highly expressed in the CNS and previous studies have further reported that the expression profile of lncRNAs is disrupted in human diseases such as neurodegenerative disorders. Since the levels of some lncRNAs change over time in the brains of patients with PD, a number of previous studies have examined their potentials as biomarkers for this brain disorder. Therefore, the main purpose of this study was to review the advances in the related literature on lncRNAs as diagnostic, therapeutic, and prognostic biomarkers for PD.

CircSTK40 contributes to recurrent implantation failure via modulating the HSP90/AKT/FOXO1 axis

Increasing evidence has revealed a close relationship between non-coding RNAs and recurrent implantation failure (RIF). However, the role of circular RNAs (circRNAs) in RIF pathogenesis remains largely unknown. Microarray analyses were used to identify the differentially expressed circRNA-circSTK40. Functional experiments, including decidualization induction and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, were performed to determine the effects of circSTK40 on human endometrial stromal cells (ESCs). The interactions between circSTK40 and proteins were investigated by RNA pull-down, RNA immunoprecipitation, and co-immunoprecipitation (coIP) assays. We observed that circSTK40 expression was upregulated in the RIF midluteal-phase endometrial samples. circSTK40 overexpression in ESCs inhibited the decidualization process but concurrently enhanced cell survival during stress. Mechanistically, circSTK40 directly bound to HSP90 and CLU, thus functioning as a scaffold to block their interactions and hinder the proteasomal degradation of HSP90. The resulting high levels of HSP90 led to the activation of the AKT pathway and downregulation of FOXO1 expression. Inhibitors of AKT (MK-2206) and HSP90 (17AAG) both abolished the effects of circSTK40 overexpression in ESCs and increased the decidualization levels in a dose-dependent manner. Our findings indicate a novel epigenetic mechanism for RIF pathogenesis involving circSTK40 activity and provide a foundation for targeted treatments in patients with low endometrial receptivity.

Genomic Landscapes of Noncoding RNAs Regulating VEGFA and VEGFC Expression in Endothelial Cells.

ABSTRACTVascular endothelial growth factors (VEGFs) are best known as key regulators of angiogenesis and lymphangiogenesis. Although VEGFs have been promising therapeutic targets for various cardiovascular diseases, their regulatory landscape in endothelial cells remains elusive. Several studies have highlighted the involvement of noncoding RNAs (ncRNAs) in the modulation of VEGF expression. In this study, we investigated the role of two classes of ncRNAs, long ncRNAs (lncRNAs) and enhancer RNAs (eRNAs), in the transcriptional regulation of VEGFA and VEGFC. By integrating genome-wide global run-on sequencing (GRO-Seq) and chromosome conformation capture (Hi-C) data, we identified putative lncRNAs and eRNAs associated with VEGFA and VEGFC genes in endothelial cells. A subset of the identified putative enhancers demonstrated regulatory activity in a reporter assay. Importantly, we demonstrate that deletion of enhancers and lncRNAs by CRISPR/Cas9 promoted significant changes in VEGFA and VEGFC expression. Transcriptome sequencing (RNA-Seq) data from lncRNA deletions showed downstream factors implicated in VEGFA- and VEGFC-linked pathways, such as angiogenesis and lymphangiogenesis, suggesting functional roles for these lncRNAs. Our study uncovers novel lncRNAs and eRNAs regulating VEGFA and VEGFC that can be targeted to modulate the expression of these important molecules in endothelial cells.

Functional roles of non-coding RNAs in atrophy

Atrophy is defined as a reduction in cell, organ, or tissue size after reaching their normal mature sizes because of loss of organelles, cytoplasmic compartments, and proteins. This process is also involved in the pathogenesis of human disorders. Inadequate nourishment, poor circulation, inadequate hormonal support, defects in nerve supply of the tissue, disproportionate induction of apoptosis in the tissue, and absence of exercise are some underlying causes of atrophy. Recently, several non-coding RNAs (ncRNAs) have been identified that regulate atrophy, thus participating in the pathobiology of related disorders such as neurodegenerative/ neuromuscular diseases, age-related muscle atrophy, and cardiac tissue atrophy. In the current review, we have focused on two classes of ncRNAs namely long ncRNAs (lncRNAs) and microRNAs (miRNAs) to unravel their participation in atrophy-associated disorders.

Dysregulation of long non-coding RNAs and their mechanisms in Huntington's disease.

Extensive alterations in gene regulatory networks are a typical characteristic of Huntington's disease (HD); these include alterations in protein-coding genes and poorly understood non-coding RNAs (ncRNAs), which are associated with pathology caused by mutant huntingtin. Long non-coding RNAs (lncRNAs) are an important class of ncRNAs involved in a variety of biological functions, including transcriptional regulation and post-transcriptional modification of many targets, and likely contributed to the pathogenesis of HD. While a number of changes in lncRNAs expression have been observed in HD, little is currently known about their functions. Here, we discuss their possible mechanisms and molecular functions, with a particular focus on their roles in transcriptional regulation. These findings give us a better insight into HD pathogenesis and may provide new targets for the treatment of this neurodegenerative disease.

Emerging Classes of Small Non-Coding RNAs With Potential Implications in Diabetes and Associated Metabolic Disorders.

Most of the sequences in the human genome do not code for proteins but generate thousands of non-coding RNAs (ncRNAs) with regulatory functions. High-throughput sequencing technologies and bioinformatic tools significantly expanded our knowledge about ncRNAs, highlighting their key role in gene regulatory networks, through their capacity to interact with coding and non-coding RNAs, DNAs and proteins. NcRNAs comprise diverse RNA species, including amongst others PIWI-interacting RNAs (piRNAs), involved in transposon silencing, and small nucleolar RNAs (snoRNAs), which participate in the modification of other RNAs such as ribosomal RNAs and transfer RNAs. Recently, a novel class of small ncRNAs generated from the cleavage of tRNAs or pre-tRNAs, called tRNA-derived small RNAs (tRFs) has been identified. tRFs have been suggested to regulate protein translation, RNA silencing and cell survival. While for other ncRNAs an implication in several pathologies is now well established, the potential involvement of piRNAs, snoRNAs and tRFs in human diseases, including diabetes, is only beginning to emerge. In this review, we summarize fundamental aspects of piRNAs, snoRNAs and tRFs biology. We discuss their biogenesis while emphasizing on novel sequencing technologies that allow ncRNA discovery and annotation. Moreover, we give an overview of genomic approaches to decrypt their mechanisms of action and to study their functional relevance. The review will provide a comprehensive landscape of the regulatory roles of these three types of ncRNAs in metabolic disorders by reporting their differential expression in endocrine pancreatic tissue as well as their contribution to diabetes incidence and diabetes-underlying conditions such as inflammation. Based on these discoveries we discuss the potential use of piRNAs, snoRNAs and tRFs as promising therapeutic targets in metabolic disorders.

The Involvement of Long Non-Coding RNAs in Bone.

A harmonious balance between osteoblast and osteoclast activity guarantees optimal bone formation and resorption, pathological conditions affecting the bone may arise. In recent years, emerging evidence has shown that epigenetic mechanisms play an important role during osteoblastogenesis and osteoclastogenesis processes, including long non-coding RNAs (lncRNAs). These molecules are a class of ncRNAs with lengths exceeding 200 nucleotides not translated into protein, that have attracted the attention of the scientific community as potential biomarkers to use for the future development of novel diagnostic and therapeutic approaches for several pathologies, including bone diseases. This review aims to provide an overview of the lncRNAs and their possible molecular mechanisms in the osteoblastogenesis and osteoclastogenesis processes. The deregulation of their expression profiles in common diseases associated with an altered bone turnover is also described. In perspective, lncRNAs could be considered potential innovative molecular biomarkers to help with earlier diagnosis of bone metabolism-related disorders and for the development of new therapeutic strategies.

Noncoding RNAs in Glioblastoma: Emerging Biological Concepts and Potential Therapeutic Implications.

Simple SummarySince the completion of the Human Genome Project, noncoding RNAs (ncRNAs) have emerged as an important class of genetic regulators. Several classes of ncRNAs, which include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs), have been shown to play important roles in controlling developmental and disease processes. In this article, we discuss the potential roles of ncRNAs in regulating glioblastoma (GBM) formation and progression as well as potential strategies to exploit the diagnostic and therapeutic potential of ncRNAs in GBM.Noncoding RNAs (ncRNAs) have emerged as a novel class of genomic regulators, ushering in a new era in molecular biology. With the advent of advanced genetic sequencing technology, several different classes of ncRNAs have been uncovered, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs), which have been linked to many important developmental and disease processes and are being pursued as clinical and therapeutic targets. Molecular phenotyping studies of glioblastoma (GBM), the most common and lethal cancer of the adult brain, revealed that several ncRNAs are frequently dysregulated in its pathogenesis. Additionally, ncRNAs regulate many important aspects of glioma biology including tumour cell proliferation, migration, invasion, apoptosis, angiogenesis, and self-renewal. Here, we present an overview of the biogenesis of the different classes of ncRNAs, discuss their biological roles, as well as their relevance to gliomagenesis. We conclude by discussing potential approaches to therapeutically target the ncRNAs in clinic.

Pathogenesis and prospects for therapeutic clinical application of noncoding RNAs in glaucoma: Systematic perspectives.

Noncoding ribonucleic acids (ncRNAs) are an increasingly studied class of RNA molecules with extensive biological activities, including important roles in human development, health, and disease. Glaucoma is a neurodegenerative disease of the retina, and one of the leading causes of blindness worldwide. However, the specific roles of ncRNAs in the development and progression of glaucoma are unclear, and related reports are fragmented. An in‐depth understanding of ncRNAs participating in the pathogenesis and progression of glaucoma would be helpful for opening up new avenues to facilitate the early diagnosis and clinical treatment. Therefore, in this review, we aimed to discuss the current research progress, the potentialfuture clinical applications and the research limitations of three critical classes of ncRNAs in glaucoma, namely microRNAs, long noncoding RNAs, and circular RNAs.

Structure of a bacterial OapB protein with its OLE RNA target gives insights into the architecture of the OLE ribonucleoprotein complex

The OLE (ornate, large, and extremophilic) RNA class is one of the most complex and well-conserved bacterial noncoding RNAs known to exist. This RNA is known to be important for bacterial responses to stress caused by short-chain alcohols, cold, and elevated Mg2+ concentrations. These biological functions have been shown to require the formation of a ribonucleoprotein (RNP) complex including at least two protein partners: OLE-associated protein A (OapA) and OLE-associated protein B (OapB). OapB directly binds OLE RNA with high-affinity and specificity and is believed to assist in assembling the functional OLE RNP complex. To provide the atomic details of OapB-OLE RNA interaction and to potentially reveal previously uncharacterized protein-RNA interfaces, we determined the structure of OapB from Bacillus halodurans alone and in complex with an OLE RNA fragment at resolutions of 1.0 Å and 2.0 Å, respectively. The structure of OapB exhibits a K-shaped overall architecture wherein its conserved KOW motif and additional unique structural elements of OapB form a bipartite RNA-binding surface that docks to the P13 hairpin and P12.2 helix of OLE RNA. These high-resolution structures elucidate the molecular contacts used by OapB to form a stable RNP complex and explain the high conservation of sequences and structural features at the OapB-OLE RNA-binding interface. These findings provide insight into the role of OapB in the assembly and biological function of OLE RNP complex and can guide the exploration of additional possible OLE RNA-binding interactions present in OapB.

Abstract PD15-01: Snord67 promotes lymph node metastasis through U6-mediated alternative splicing in breast cancer

Abstract Background: While the presence of lymph node (LN) metastases in solid tumor malignancies is clinically significant and associated with increased risk for distant metastases, there is little evidence that lymphatic metastasis is distinct from hematogenous dissemination. Recent studies showed that cancer cells in LNs can directly give rise to distant metastases, but the mechanisms behind how cancer cells exit lymph nodes to establish distant metastases is still unknown. Materials and Methods: We developed an immunocompetent mouse model of lymph node metastasis using the 4T1 murine breast cancer cell line. In this model, 4T1 cells micro-surgically injected into axillary lymph nodes (AxLN) are capable of spontaneously establishing distant metastases. We then performed microarray analyses of subclones derived from MFP tumors, AxLN-injected tumors (AxLN), and lung metastases that arose from AxLN-injected tumors (AxLN-LuM) to evaluate for non-coding RNAs (ncRNAs) that were differentially expressed in AxLN tumors. Results: Microarray analyses of ncRNAs expressed in MFP, AxLN, and AxLN-LuM subclones showed that a class of ncRNAs, small nucleolar RNAs (snoRNAs), were enriched in AxLN tumors compared to MFP and AxLN-LuM. We identified the snoRNA SNORD67 as a key regulator of LN metastasis. Knockout of SNORD67 by both CRISPR and antisense oligonucleotide (ASO) resulted in significantly decreased LN tumor growth and subsequent development of distant metastases. This was at least in-part due to loss of targeted 2’-O-methylation of the small nuclear RNA U6, a component of the spliceosome. RNA-Seq analyses revealed distinct alternative splicing in SNORD67 knockouts. Using rapid autopsy breast cancer cases, we found that matched primary tumor and LN metastases revealed similar alternatively spliced genes, including several genes with previously described cancer-promoting splice variants. Conclusions: Small nucleolar RNAs (snoRNAs) have long been regarded as “housekeeping genes”, important for ribosomal biogenesis and protein synthesis. However, there is increasing evidence that this largely ignored class of non-coding RNAs (ncRNAs) also have wide-ranging, non-canonical functions in diseases, including cancer. SnoRNAs have been shown to have both oncogenic and tumor suppressor roles, yet whether snoRNAs regulate metastasis is unknown. Here we show that expression of certain snoRNAs are enriched in lymph node (LN) metastases in a micro-surgical, immune-competent mouse model of breast cancer. Moreover, our results show that SNORD67 is critical for growth of LN metastases and subsequent spread to distant metastases, and suggest that snoRNA-guided modifications of the spliceosome represent a previously unappreciated, yet targetable pathway in cancer. Citation Format: Yvonne Chao, Yinzhou Zhu, Hannah J Wiedner, Yi-Hsuan Tsai, Lily Wilkinson, Alessandro Porrello, Amanda ED Van Swearingen, Lisa Carey, Jimena Giudice, Christopher L Holley, Chad V Pecot. Snord67 promotes lymph node metastasis through U6-mediated alternative splicing in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD15-01.

Abundantly expressed class of noncoding RNAs conserved through the multicellular evolution of dictyostelid social amoebas.

Aggregative multicellularity has evolved multiple times in diverse groups of eukaryotes, exemplified by the well-studied development of dictyostelid social amoebas, for example, Dictyostelium discoideum. However, it is still poorly understood why multicellularity emerged in these amoebas while the majority of other members of Amoebozoa are unicellular. Previously, a novel type of noncoding RNA, Class I RNAs, was identified in D. discoideum and shown to be important for normal multicellular development. Here, we investigated Class I RNA evolution and its connection to multicellular development. We identified a large number of new Class I RNA genes by constructing a covariance model combined with a scoring system based on conserved upstream sequences. Multiple genes were predicted in representatives of each major group of Dictyostelia and expression analysis confirmed that our search approach identifies expressed Class I RNA genes with high accuracy and sensitivity and that the RNAs are developmentally regulated. Further studies showed that Class I RNAs are ubiquitous in Dictyostelia and share highly conserved structure and sequence motifs. In addition, Class I RNA genes appear to be unique to dictyostelid social amoebas because they could not be identified in outgroup genomes, including their closest known relatives. Our results show that Class I RNA is an ancient class of ncRNAs, likely to have been present in the last common ancestor of Dictyostelia dating back at least 600 million years. Based on previous functional analyses and the presented evolutionary investigation, we hypothesize that Class I RNAs were involved in evolution of multicellularity in Dictyostelia.

Downregulated hsa_circ_0036988 promotes proliferation and metastasis in oral squamous cell carcinoma.

As a novel class of endogenous ncRNAs, Circular RNAs (circRNAs) have been verified to be involved in the carcinogenesis and tumor progression. This study aimed to investigate the potential function of a candidate circRNA hsa_circ_0036988 in oral squamous cell carcinoma (OSCC). The altered expression of hsa_circ_0036988 was validated by quantitative real-time polymerase chain reaction (qRT-PCR) in OSCC samples and OSCC cell lines. The associations between the levels of hsa_circ_0036988 and the clinicopathological features were statistically analysed. The function of hsa_circ_0036988 in OSCC were evaluated via a series of in vitro experiments by using constructed plasmids or siRNA. Western blotting assays were conducted to evaluate changes in protein expression levels. Hsa_circ_0036988 was significantly downregulated in OSCC tissues compared with adjacent normal tissues. While low expression of hsa_circ_0036988 was highly correlated with lymph nodes metastasis. Overexpression or knockdown of hsa_circ_0036988 significantly affected the proliferation, migration and invasion of OSCC cells. Furthermore, the altered expression of hsa_circ_0036988 have an impact on the epithelial-to-mesenchymal transition (EMT)-related protein expression levels. Our findings indicated that hsa_circ_0036988 may affect cell proliferation, migration and invasion by regulating EMT progress, which might provide a therapeutic strategy for the treatment of OSCC.

Circular RNA in pancreatic cancer: a novel avenue for the roles of diagnosis and treatment.

Pancreatic cancer (PC), an important cause of cancer-related deaths worldwide, is one of the most malignant cancers characterized by a dismal prognosis. Circular RNAs (circRNAs), a class of endogenous ncRNAs with unique covalently closed loops, have attracted great attention in regard to various diseases, especially cancers. Compelling studies have suggested that circRNAs are aberrantly expressed in different cancer tissues and cell types, including PC. More specifically, circRNAs can modify the proliferation, progression, tumorigenesis and chemosensitivity of PC, and some circRNAs could serve as biomarkers for diagnosis and prognosis. Herein, we summarize what is currently known to be related to the biogenesis, functions and potential roles of human circRNAs in PC and their application prospects for PC clinical treatments.

Fluorescence In Situ Hybridization of Small Non-Coding RNAs.

The determination of the cellular localization of a noncoding RNA (ncRNA) is highly helpful to decipher its function. RNA-FISH is a powerful method to detect specific RNAs in fixed cells. It allows both localization and quantification of RNA molecules within individual cells and tissues. Refined RNA-FISH methods have also been developed to determine RNA transcription and degradation rates. This chapter describes an RNA-FISH protocol that we developed to study the expression and localization of satellite III (SATIII) RNAs. This specific class of ncRNAs is expressed in response to various cellular stresses, including heat shock. The protocol is based on the use of a biotinylated LNA probe subsequently detected by a Streptavidin, Alexa Fluor® 488 conjugate. A protocol allowing efficient coupling of RNA-FISH and protein detection by immunofluorescence is also described as well as the bioinformatics pipeline, Substructure Analyzer, we recently developed to automate fluorescence signal analysis.

Computational methods for annotation of plant regulatory non-coding RNAs using RNA-seq.

Plant transcriptome encompasses numerous endogenous, regulatory non-coding RNAs (ncRNAs) that play a major biological role in regulating key physiological mechanisms. While studies have shown that ncRNAs are extremely diverse and ubiquitous, the functions of the vast majority of ncRNAs are still unknown. With ever-increasing ncRNAs under study, it is essential to identify, categorize and annotate these ncRNAs on a genome-wide scale. The use of high-throughput RNA sequencing (RNA-seq) technologies provides a broader picture of the non-coding component of transcriptome, enabling the comprehensive identification and annotation of all major ncRNAs across samples. However, the detection of known and emerging class of ncRNAs from RNA-seq data demands complex computational methods owing to their unique as well as similar characteristics. Here, we discuss major plant endogenous, regulatory ncRNAs in an RNA sample followed by computational strategies applied to discover each class of ncRNAs using RNA-seq. We also provide a collection of relevant software packages and databases to present a comprehensive bioinformatics toolbox for plant ncRNA researchers. We assume that the discussions in this review will provide a rationale for the discovery of all major categories of plant ncRNAs.

The Impact of Diet on the Involvement of Non-Coding RNAs, Extracellular Vesicles, and Gut Microbiome-Virome in Colorectal Cancer Initiation and Progression.

Cancer is the major cause of morbidity and mortality in the world today. The third most common cancer and which is most diet related is colorectal cancer (CRC). Although there is complexity and limited understanding in the link between diet and CRC, the advancement in research methods have demonstrated the involvement of non-coding RNAs (ncRNAs) as key regulators of gene expression. MicroRNAs (miRNAs) which are a class of ncRNAs are key players in cancer related pathways in the context of dietary modulation. The involvement of ncRNA in cancer progression has recently been clarified throughout the last decade. ncRNAs are involved in biological processes relating to tumor onset and progression. The advances in research have given insights into cell to cell communication, by highlighting the pivotal involvement of extracellular vesicle (EV) associated-ncRNAs in tumorigenesis. The abundance and stability of EV associated ncRNAs act as a new diagnostic and therapeutic target for cancer. The understanding of the deranging of these molecules in cancer can give access to modulating the expression of the ncRNAs, thereby influencing the cancer phenotype. Food derived exosomes/vesicles (FDE) are gaining interest in the implication of exosomes in cell-cell communication with little or no understanding to date on the role FDE plays. There are resident microbiota in the colon; to which the imbalance in the normal intestinal occurrence leads to chronic inflammation and the production of carcinogenic metabolites that lead to neoplasm. Limited studies have shown the implication of various types of microbiome in CRC incidence, without particular emphasis on fungi and protozoa. This review discusses important dietary factors in relation to the expression of EV-associated ncRNAs in CRC, the impact of diet on the colon ecosystem with particular emphasis on molecular mechanisms of interactions in the ecosystem, the influence of homeostasis regulators such as glutathione, and its conjugating enzyme-glutathione S-transferase (GST) polymorphism on intestinal ecosystem, oxidative stress response, and its relationship to DNA adduct fighting enzyme-0-6-methylguanine-DNA methyltransferase. The understanding of the molecular mechanisms and interaction in the intestinal ecosystem will inform on the diagnostic, preventive and prognosis as well as treatment of CRC.

Increased processing of SINE B2 ncRNAs unveils a novel type of transcriptome deregulation in amyloid beta neuropathology.

The functional importance of many non-coding RNAs (ncRNAs) generated by repetitive elements and their connection with pathologic processes remains elusive. B2 RNAs, a class of ncRNAs of the B2 family of SINE repeats, mediate through their processing the transcriptional activation of various genes in response to stress. Here, we show that this response is dysfunctional during amyloid beta toxicity and pathology in the mouse hippocampus due to increased levels of B2 RNA processing, leading to constitutively elevated B2 RNA target gene expression and high Trp53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in hippocampal cells and is activated during amyloid toxicity, accelerating the processing of SINE RNAs and gene hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer's disease (AD).