RESUMEN

In recent years, the function of noncoding RNAs (ncRNAs) as regulatory molecules of cell physiology has begun to be better understood. Advances in viral molecular biology have shown that host ncRNAs, cellular factors, and virus-derived ncRNAs and their interplay are strongly disturbed during viral infections. Nevertheless, the folding of RNA virus genomes has also been identified as a critical factor in regulating canonical and non-canonical functions. Due to the influence of host ncRNAs and the structure of RNA viral genomes, complex molecular and cellular processes in infections are modulated. We propose three main categories to organize the current information about RNA-RNA interactions in some well-known human viruses. The first category shows examples of host ncRNAs associated with the immune response triggered in viral infections. Even though miRNAs introduce a standpoint, they are briefly presented to keep researchers moving forward in uncovering other RNAs. The second category outlines interactions between virus-host ncRNAs, while the third describes how the structure of the RNA viral genome serves as a scaffold for processing virus-derived RNAs. Our grouping may provide a comprehensive framework to classify ncRNA-host-cell interactions for emerging viruses and diseases. In this sense, we introduced them to organize DENV-host-cell interactions.

Asunto(s)

RESUMEN

In recent years, a population of small RNA fragments derived from non-coding RNAs (sfd-RNAs) has gained significant interest due to its functional and structural resemblance to miRNAs, adding another level of complexity to our comprehension of small-RNA-mediated gene regulation. Despite this, scientists need more tools to test the differential expression of sfd-RNAs since the current methods to detect miRNAs may not be directly applied to them. The primary reasons are the lack of accurate small RNA and ncRNA annotation, the multi-mapping read (MMR) placement, and the multicopy nature of ncRNAs in the human genome. To solve these issues, a methodology that allows the detection of differentially expressed sfd-RNAs, including canonical miRNAs, by using an integrated copy-number-corrected ncRNA annotation was implemented. This approach was coupled with sixteen different computational strategies composed of combinations of four aligners and four normalization methods to provide a rank-order of prediction for each differentially expressed sfd-RNA. By systematically addressing the three main problems, we could detect differentially expressed miRNAs and sfd-RNAs in dengue virus-infected human dermal microvascular endothelial cells. Although more biological evaluations are required, two molecular targets of the hsa-mir-103a and hsa-mir-494 (CDK5 and PI3/AKT) appear relevant for dengue virus (DENV) infections. Here, we performed a comprehensive annotation and differential expression analysis, which can be applied in other studies addressing the role of small fragment RNA populations derived from ncRNAs in virus infection.

RESUMEN

BACKGROUND: In view of discordance consisting in different reports, a meta-analysis was conducted to comprehensively evaluate the diagnostic efficacy of exosomal noncoding RNAs (ncRNAs) in blood and urine in the detection of bladder cancer. METHODS: Eligible studies were acquired by systematic retrieval through PubMed, Cochrane Library, and Embase. The pooled diagnostic efficacy was appraised by reckoning the area under the summary receiver operating characteristic (SROC) curve. The latent sources of heterogeneity were probed by subgroup analyses and meta-regression. STATA 12.0, Meta-DiSc 1.4, and RevMan 5.3 were applied to carry out all statistical analyses and plots. RESULTS: A total of 46 studies from 15 articles comprising 2622 controls and 3015 bladder cancer patients were included in our meta-analysis. Exosomal ncRNAs in blood and urine represented relatively satisfactory diagnostic efficacy in detecting bladder cancer, with a pooled sensitivity of 0.75, a specificity of 0.79, and an area under the SROC curve (AUC) of 0.84. Exosomal microRNAs (miRNAs) exhibited better diagnostic value with a pooled AUC of 0.91 than that of exosomal long noncoding RNAs (lncRNAs). To some extent, the heterogeneity among studies was induced by exosomal ncRNA types (miRNA or lncRNA), exosomal ncRNA profiling (single- or multiple-ncRNA), sample size, specimen types, and ethnicity. CONCLUSION: Exosomal ncRNAs in blood and urine may play a vital role in diagnosing bladder cancer as prospective noninvasive biomarkers; nonetheless, their clinical performance needs to be confirmed by further massive proactive researches.

Asunto(s)

RESUMEN

Leprosy is an infectious disease primarily caused by the obligate intracellular parasite Mycobacterium leprae. Although it has been considered eradicated in many countries, leprosy continues to be a health issue in developing nations. Besides the social stigma associated with it, individuals affected by leprosy may experience nerve damage leading to physical disabilities if the disease is not properly treated or early diagnosed. Leprosy is recognized as a complex disease wherein socioenvironmental factors, immune response, and host genetics interact to contribute to its development. Recently, a new field of study called epigenetics has emerged, revealing that the immune response and other mechanisms related to infectious diseases can be influenced by noncoding RNAs. This review aims to summarize the significant advancements concerning non-coding RNAs in leprosy, discussing the key perspectives on this novel approach to comprehending the pathophysiology of the disease and identifying molecular markers. In our view, investigations on non-coding RNAs in leprosy hold promise and warrant increased attention from researches in this field.

RESUMEN

Testicular cancer is the most prevalent tumor among males aged 15 to 35, resulting in a significant number of newly diagnosed cases and fatalities annually. Non-coding RNAs (ncRNAs) have emerged as key regulators in various cellular processes and pathologies, including testicular cancer. Their involvement in gene regulation, coding, decoding, and overall gene expression control suggests their potential as targets for alternative treatment approaches for this type of cancer. Furthermore, epigenetic modifications, such as histone modifications, DNA methylation, and the regulation by microRNA (miRNA), have been implicated in testicular tumor progression and treatment response. Epigenetics may also offer critical insights for prognostic evaluation and targeted therapies in patients with testicular germ cell tumors (TGCT). This comprehensive review aims to present the latest discoveries regarding the involvement of some proteins and ncRNAs, mainly miRNAs and lncRNA, in the epigenetic aspect of testicular cancer, emphasizing their relevance in pathogenesis and their potential, given the fact that their specific expression holds promise for prognostic evaluation and targeted therapies.

Asunto(s)

RESUMEN

Breast cancer (BC) leads to the most amounts of deaths among women. Chemo-, endocrine-, and targeted therapies are the mainstay drug treatments for BC in the clinic. However, drug resistance is a major obstacle for BC patients, and it leads to poor prognosis. Accumulating evidences suggested that noncoding RNAs (ncRNAs) are intricately linked to a wide range of pathological processes, including drug resistance. Till date, the correlation between drug resistance and ncRNAs is not completely understood in BC. Herein, we comprehensively summarized a dysregulated ncRNAs landscape that promotes or inhibits drug resistance in chemo-, endocrine-, and targeted BC therapies. Our review will pave way for the effective management of drug resistance by targeting oncogenic ncRNAs, which, in turn will promote drug sensitivity of BC in the future.

Asunto(s)

RESUMEN

Complex molecular mechanisms define our responses to environmental stimuli. Beyond the DNA sequence itself, epigenetic machinery orchestrates changes in gene expression induced by diet, physical activity, stress and pollution, among others. Importantly, nutrition has a strong impact on epigenetic players and, consequently, sustains a promising role in the regulation of cellular responses such as oxidative stress. As oxidative stress is a natural physiological process where the presence of reactive oxygen-derived species and nitrogen-derived species overcomes the uptake strategy of antioxidant defenses, it plays an essential role in epigenetic changes induced by environmental pollutants and culminates in signaling the disruption of redox control. In this review, we present an update on epigenetic mechanisms induced by environmental factors that lead to oxidative stress and potentially to pathogenesis and disease progression in humans. In addition, we introduce the microenvironment factors (physical contacts, nutrients, extracellular vesicle-mediated communication) that influence the epigenetic regulation of cellular responses. Understanding the mechanisms by which nutrients influence the epigenome, and thus global transcription, is crucial for future early diagnostic and therapeutic efforts in the field of environmental medicine.

RESUMEN

Obesity is an alarming disease that favors the upset of other illnesses and enhances mortality. It is spreading fast worldwide may affect more than 1 billion people by 2030. The imbalance between excessive food ingestion and less energy expenditure leads to pathological adipose tissue expansion, characterized by increased production of proinflammatory mediators with harmful interferences in the whole organism. Bone tissue is one of those target tissues in obesity. Bone is a mineralized connective tissue that is constantly renewed to maintain its mechanical properties. Osteoblasts are responsible for extracellular matrix synthesis, while osteoclasts resorb damaged bone, and the osteocytes have a regulatory role in this process, releasing growth factors and other proteins. A balanced activity among these actors is necessary for healthy bone remodeling. In obesity, several mechanisms may trigger incorrect remodeling, increasing bone resorption to the detriment of bone formation rates. Thus, excessive weight gain may represent higher bone fragility and fracture risk. This review highlights recent insights on the central mechanisms related to obesity-associated abnormal bone. Publications from the last ten years have shown that the main molecular mechanisms associated with obesity and bone loss involve: proinflammatory adipokines and osteokines production, oxidative stress, non-coding RNA interference, insulin resistance, and changes in gut microbiota. The data collection unveils new targets for prevention and putative therapeutic tools against unbalancing bone metabolism during obesity.

Asunto(s)

RESUMEN

RNA sequencing (RNA-Seq) and mass-spectrometry-based proteomics data are often integrated in proteogenomic studies to assist in the prediction of eukaryote genome features, such as genes, splicing, single-nucleotide (SNVs), and single-amino-acid variants (SAAVs). Most genomes of parasite nematodes are draft versions that lack transcript- and protein-level information and whose gene annotations rely only on computational predictions. Angiostrongylus costaricensis is a roundworm species that causes an intestinal inflammatory disease, known as abdominal angiostrongyliasis (AA). Currently, there is no drug available that acts directly on this parasite, mostly due to the sparse understanding of its molecular characteristics. The available genome of A. costaricensis, specific to the Costa Rica strain, is a draft version that is not supported by transcript- or protein-level evidence. This study used RNA-Seq and MS/MS data to perform an in-depth annotation of the A. costaricensis genome. Our prediction improved the reference annotation with (a) novel coding and non-coding genes; (b) pieces of evidence of alternative splicing generating new proteoforms; and (c) a list of SNVs between the Brazilian (Crissiumal) and the Costa Rica strain. To the best of our knowledge, this is the first time that a multi-omics approach has been used to improve the genome annotation of A. costaricensis. We hope this improved genome annotation can assist in the future development of drugs, kits, and vaccines to treat, diagnose, and prevent AA caused by either the Brazil strain (Crissiumal) or the Costa Rica strain.

RESUMEN

Colorectal cancer (CRC) is the third most common cancer in the world today, and its incidence and mortality rates are increasing every year. The ease of proliferation and metastasis of CRC has long been an important reason for its high mortality rate. Exosomes serve as key mediators that mediate communication between tumor cells and various other cells. Non-coding RNAs (ncRNAs) have been shown to play a key role in apoptosis, immunosuppression and proliferation metastasis in cancer. ncRNAs are loaded on exosomes and initiate the onset of metastasis by promoting epithelial-mesenchymal transition (EMT) at the primary site of the tumor. Meanwhile, exosome-derived ncRNAs construct a pre-metastatic niche (PMN) for CRC metastasis by forming an inflammatory microenvironment in distant organs, immunosuppression, and promoting angiogenesis and remodeling of the extracellular matrix. Here, we summarize the specific mechanisms associated with exosome-derived ncRNAs promoting local invasion and metastasis in CRC. Finally, we focus on their value for clinical application in future CRC diagnosis and treatment.

Asunto(s)

RESUMEN

Penile cancer (PC) still presents a health threat for developing countries, in particular Brazil. Despite this, little progress has been made on the study of markers, including molecular ones, that can aid in the correct management of the patient, especially concerning lymphadenectomy. As in other neoplasms, non-coding RNAs (ncRNAs) have been investigated for penile cancer, with emphasis on microRNAs, piRNAs (PIWI-interacting small RNAs), and long non-coding RNAs (LncRNAs). In this context, this review aims to assemble the available knowledge on non-coding RNA linked in PC, contributing to our understanding of the penile carcinogenesis process and addressing their clinical relevance. ncRNAs are part of the novel generation of biomarkers, with high potential for diagnosis and prognosis, orientating the type of treatment. Furthermore, its versatility regarding the use of paraffin samples makes it possible to carry out retrospective studies.

RESUMEN

Autophagy is a highly conserved multistep lysosomal degradation process in which cellular components are localized to autophagosomes, which subsequently fuse with lysosomes to degrade the sequestered contents. Autophagy serves to maintain cellular homeostasis. There is a close relationship between autophagy and tumor progression, which provides opportunities for the development of anticancer therapeutics that target the autophagy pathway. In this review, we analyze the effects of human papillomavirus (HPV) E5, E6, and E7 oncoproteins on autophagy processes in cervical cancer development. Inhibition of the expression or the activity of E5, E6, and E7 can induce autophagy in cells expressing HPV oncogenes. Thus, E5, E6, and E7 oncoproteins target autophagy during HPV-associated carcinogenesis. Furthermore, noncoding RNA (ncRNA) expression profiling in cervical cancer has allowed the identification of autophagy-related ncRNAs associated with HPV. Autophagy-related genes are essential drivers of autophagy and are regulated by ncRNAs. We review the existing evidence regarding the role of autophagy-related proteins, the function of HPV E5, E6, and E7 oncoproteins, and the effects of noncoding RNA on autophagy regulation in the setting of cervical carcinogenesis. By characterizing the mechanisms behind the dysregulation of these critical factors and their impact on host cell autophagy, we advance understanding of the relationship between autophagy and progression from HPV infection to cervical cancer, and highlight pathways that can be targeted in preventive and therapeutic strategies against cervical cancer.

Asunto(s)

RESUMEN

The Epstein-Barr Virus (EBV) is a gammaherpesvirus involved in the etiopathogenesis of a variety of human cancers, mostly of lymphoid and epithelial origin. The EBV infection participates in both cell transformation and tumor progression, also playing an important role in subverting immune responses against cancers. The homeostasis of the immune system is tightly regulated by inhibitory mechanisms affecting key immune effectors, such as T lymphocytes and NK cells. Collectively known as immune checkpoints, these mechanisms rely on a set of cellular receptors and ligands. These molecules may be candidate targets for immune checkpoints blockade-an emergent and promising modality of immunotherapy already proven to be valuable for a variety of human cancers. The EBV was lately suspected to interfere with the expression of immune checkpoint molecules, notably PD-1 and its ligands, found to be overexpressed in cases of Hodgkin lymphoma, nasopharyngeal, and gastric adenocarcinomas associated with the viral infection. Even though there is compelling evidence showing that the EBV interferes with other immune checkpoint regulators (e.g., CTLA-4, LAG-3, TIM-3, and VISTA), the published data are still scarce. Herein, we discuss the current state of the knowledge on how the EBV interferes with the activity of immune checkpoints regulators, as well as its implications considering the immune checkpoints blockade for clinical management of the EBV-associated malignancies, notably lymphomas.

Asunto(s)

RESUMEN

Gracilariales is a clade of florideophycean red macroalgae known for being the main source of agar. We present a de novo genome assembly and annotation of Gracilaria domingensis, an agarophyte alga with flattened thallus widely distributed along Central and South American Atlantic intertidal zones. In addition to structural analysis, an organizational comparison was done with other Rhodophyta genomes. The nuclear genome has 78 Mbp, with 11,437 predicted coding genes, 4,075 of which did not have hits in sequence databases. We also predicted 1,567 noncoding RNAs, distributed in 14 classes. The plastid and mitochondrion genome structures were also obtained. Genes related to agar synthesis were identified. Genes for type II galactose sulfurylases could not be found. Genes related to ascorbate synthesis were found. These results suggest an intricate connection of cell wall polysaccharide synthesis and the redox systems through the use of L-galactose in Rhodophyta. The genome of G. domingensis should be valuable to phycological and aquacultural research, as it is the first tropical and Western Atlantic red macroalgal genome to be sequenced.

Asunto(s)

RESUMEN

Recent advances in the transcriptomics, translatomics, and proteomics have led us to the exciting new world of functional endogenous microproteins. These microproteins have a small size and are derived from small open reading frames (smORFs) of RNAs previously annotated as non-coding (e.g. lncRNAs and circRNAs) as well as from untranslated regions and canonical mRNAs. The presence of these microproteins reveals a much larger translatable portion of the genome, shifting previously defined dogmas and paradigms. These findings affect our view of organisms as a whole, including skeletal muscle tissue. Emerging evidence demonstrates that several smORF-derived microproteins play crucial roles during muscle development (myogenesis), maintenance, and regeneration, as well as lipid and glucose metabolism and skeletal muscle bioenergetics. These microproteins are also involved in processes including physical activity capacity, cellular stress, and muscular-related diseases (i.e. myopathy, cachexia, atrophy, and muscle wasting). Given the role of these small proteins as important key regulators of several skeletal muscle processes, there are rich prospects for the discovery of new microproteins and possible therapies using synthetic microproteins.

Asunto(s)

RESUMEN

The identification and characterization of non-coding RNAs (ncRNAs) in prokaryotes is an important step in the study of the interaction of these molecules with mRNAs-or target proteins, in the post-transcriptional regulation process. Here, we describe one of the main in silico prediction methods in prokaryotes, using the TargetRNA2 tool to predict target mRNAs.

Asunto(s)

RESUMEN

Colorectal cancer (CRC) is one of the most common malignant tumors, and a large number of patients are diagnosed and die every year. Due to the lack of appropriate diagnosis, prediction and treatment, early diagnosis rate of CRC is low and the prognosis is poor. Studies have found that abnormally expressed non-coding RNAs (ncRNAs) (including microRNAs (miRNAs), circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs),etc.) play an important regulatory role in the occurrence and development of CRC. Some studies have shown that they are stable in the blood and can be detected repeatedly. They are expected to be non-invasive biomarkers for early diagnosis, prognosis evaluation, and prediction of drug sensitivity of CRC, as well as potential applications in the treatment of CRC.

Asunto(s)

RESUMEN

Coffea canephora grains are highly traded commodities worldwide. Non-coding RNAs (ncRNAs) are transcriptional products involved in genome regulation, environmental responses, and plant development. There is not an extensive genome-wide analysis that uncovers the ncRNA portion of the C. canephora genome. This study aimed to provide a curated characterization of six ncRNA classes in the Coffea canephora genome. For this purpose, we employed a combination of similarity-based and structural-based computational approaches with stringent curation. Candidate ncRNA loci had expression evidence analyzed using sRNA-seq libraries. We identified 7455 ncRNA loci (6976 with transcriptional evidence) in the C. canephora genome. This comprised of total 115 snRNAs, 1031 snoRNAs, 92 miRNA precursors, 602 tRNAs, 72 rRNAs, and 5064 lncRNAs. For miRNAs, we identified 159 putative high-confidence targets. This study was the most extensive genomic catalog of curated ncRNAs in the Coffea genus. This data might help elaborating more robust hypotheses in future comparative genomic studies as well as gene regulation and genome dynamics, helping to understand the molecular basis of domestication, environmental adaptation, resistance to pests and diseases, and coffee productivity.

RESUMEN

Oyster production is an economic activity of great interest worldwide. Recently, oysters have been suffering significant mortalities from OsHV-1infection, which has resulted in substantial economic loses in several countries around the world. Understanding viral pathogenicity mechanisms is of central importance for the establishment of disease control measures. Thus, the present work aimed to identify and characterize miRNAs from OsHV-1 as well as to predict their target transcripts in the virus and the host. OsHV-1 genome was used for the in silico discovery of pre-miRNAs. Subsequently, viral and host target transcripts of the OsHV-1 miRNAs were predicted according to the base pairing interaction between mature miRNAs and mRNA 3' untranslated regions (UTRs). Six unique pre-miRNAs were found in different regions of the viral genome, ranging in length from 85 to 172 nucleotides. A complex network of self-regulation of viral gene expression mediated by the miRNAs was identified. These sequences also seem to have a broad ability to regulate the expression of host immune-related genes, especially those associated with pathogen recognition. Our results suggest that OsHV-1 encodes miRNAs with important functions in the infection process, inducing self-regulation of viral transcripts, as well as affecting the regulation of Pacific oyster transcripts related to immunity. Understanding the molecular basis of host-pathogen interactions can help mitigate the recurrent events of oyster mass mortalities by OsHV-1 observed worldwide.

Asunto(s)

RESUMEN

Insects are the largest animal group on Earth both in biomass and diversity. Their outstanding success has inspired genetics and developmental research, allowing the discovery of dynamic process explaining extreme phenotypic plasticity and canalization. Epigenetic molecular mechanisms (EMMs) are vital for several housekeeping functions in multicellular organisms, regulating developmental, ontogenetic trajectories and environmental adaptations. In Insecta, EMMs are involved in the development of extreme phenotypic divergences such as polyphenisms and eusocial castes. Here, we review the history of this research field and how the main EMMs found in insects help to understand their biological processes and diversity. EMMs in insects confer them rapid response capacity allowing insect either to change with plastic divergence or to keep constant when facing different stressors or stimuli. EMMs function both at intra as well as transgenerational scales, playing important roles in insect ecology and evolution. We discuss on how EMMs pervasive influences in Insecta require not only the control of gene expression but also the dynamic interplay of EMMs with further regulatory levels, including genetic, physiological, behavioral, and environmental among others, as was earlier proposed by the Probabilistic Epigenesis model and Developmental System Theory.

Asunto(s)