Methylation of subtelomeric chromatin modifies the expression of the lncRNA TERRA, disturbing telomere homeostasis

The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability

The Clinical Utility of lncRNAs and Their Application as Molecular Biomarkers in Breast Cancer

Given their tumor-specific and stage-specific gene expression, long non-coding RNAs (lncRNAs) have demonstrated to be potential molecular biomarkers for diagnosis, prognosis, and treatment response. Particularly, the lncRNAs DSCAM-AS1 and GATA3-AS1 serve as examples of this because of their high subtype-specific expression profile in luminal B-like breast cancer. This makes them candidates to use as molecular biomarkers in clinical practice. However, lncRNA studies in breast cancer are limited in sample size and are restricted to the determination of their biological function, which represents an obstacle for its inclusion as molecular biomarkers of clinical utility. Nevertheless, due to their expression specificity among diseases, such as cancer, and their stability in body fluids, lncRNAs are promising molecular biomarkers that could improve the reliability, sensitivity, and specificity of molecular techniques used in clinical diagnosis. The development of lncRNA-based diagnostics and lncRNA-based therapeutics will be useful in routine medical practice to improve patient clinical management and quality of life

Transcriptomics and RNA-Based Therapeutics as Potential Approaches to Manage SARS-CoV-2 Infection

SARS-CoV-2 is a coronavirus family member that appeared in China in December 2019 and caused the disease called COVID-19, which was declared a pandemic in 2020 by the World Health Organization. In recent months, great efforts have been made in the field of basic and clinical research to understand the biology and infection processes of SARS-CoV-2. In particular, transcriptome analysis has contributed to generating new knowledge of the viral sequences and intracellular signaling pathways that regulate the infection and pathogenesis of SARS-CoV-2, generating new information about its biology. Furthermore, transcriptomics approaches including spatial transcriptomics, single-cell transcriptomics and direct RNA sequencing have been used for clinical applications in monitoring, detection, diagnosis, and treatment to generate new clinical predictive models for SARS-CoV-2. Consequently, RNA-based therapeutics and their relationship with SARS-CoV-2 have emerged as promising strategies to battle the SARS-CoV-2 pandemic with the assistance of novel approaches such as CRISPR-CAS, ASOs, and siRNA systems. Lastly, we discuss the importance of precision public health in the management of patients infected with SARS-CoV-2 and establish that the fusion of transcriptomics, RNA-based therapeutics, and precision public health will allow a linkage for developing health systems that facilitate the acquisition of relevant clinical strategies for rapid decision making to assist in the management and treatment of the SARS-CoV-2-infected population to combat this global public health problem

Genomic Profile in a Non-Seminoma Testicular Germ-Cell Tumor Cohort Reveals a Potential Biomarker of Sensitivity to Platinum-Based Therapy

SIMPLE SUMMARY: Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Incidence and mortality of this disease has remained unchanged in Latin populations unlike the rest of the world. To date, the search for genetic variants in our population remains unexplored. The aim of this study is to identify predictive biomarkers of resistance to platinum-based therapy, whether general or specific to the Latin population. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. However, we identified amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population. ABSTRACT: Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population

Molecular features of influenza A (H1N1)pdm09 prevalent in Mexico during winter seasons 2012-2014

<div><p>Since the emergence of the pandemic H1N1pdm09 virus in Mexico and California, biannual increases in the number of cases have been detected in Mexico. As observed in previous seasons, pandemic A/H1N1 09 virus was detected in severe cases during the 2011–2012 winter season and finally, during the 2013–2014 winter season it became the most prevalent influenza virus. Molecular and phylogenetic analyses of the whole viral genome are necessary to determine the antigenic and pathogenic characteristics of influenza viruses that cause severe outcomes of the disease. In this paper, we analyzed the evolution, antigenic and genetic drift of Mexican isolates from 2009, at the beginning of the pandemic, to 2014. We found a clear variation of the virus in Mexico from the 2011–2014 season due to different markers and in accordance with previous reports. In this study, we identified 13 novel substitutions with important biological effects, including virulence, T cell epitope presented by MHC and host specificity shift and some others substitutions might have more than one biological function. The systematic monitoring of mutations on whole genome of influenza A pH1N1 (2009) virus circulating at INER in Mexico City might provide valuable information to predict the emergence of new pathogenic influenza virus</p></div

Analysis of detected substitutions at or beside antigenic sites of HA, of Mexican isolates from 2011–12 and 2013–14.

<p>The analysis of substitutions at HA was made using sequence California/07/2009 as reference to establish the changes at the antigenic sites and in their neighboring positions. The antigenic sites are shaded and identified by colours. Blue is for Cb site, pink is for Sa site, Green is for Ca site and yellow is for Sb site. The amino acids in red represent changes detected in sequences of isolates from 2011–12 and white represent the changes detected in isolates from 2013–14.</p

Maximum likelihood (ML) phylogenetic tree for the HA segment.

<p>ML trees from 1200–1300 A(H1N1)pdm09 viruses deposited in GenBank from 2009 to 2014 were produced with 1,000 bootstrap replicates, for the indicated genetic segments as explained in the Methods section. Phylogenetic tree included 7–17 sequences from 2012 (PB2, 10; PB1, 8; PA, 7; HA, 10; NP, 11; NA, 8; M, 17 and NS, 17), 3 sequences from 2013 and 7 sequences from 2014; obtained for this study. Red dots at nodes show branches with 50% bootstrap support leading to the 2014 sequences described in this work. Trees for the rest of the viral genome segments can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180419#pone.0180419.s002" target="_blank">S1</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180419#pone.0180419.s008" target="_blank">S7</a> Figs (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180419#pone.0180419.s002" target="_blank">S1 Fig</a> <b>NA</b>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180419#pone.0180419.s003" target="_blank">S2 Fig</a> <b>PB2</b>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180419#pone.0180419.s004" target="_blank">S3 Fig</a> <b>PB2</b>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180419#pone.0180419.s005" target="_blank">S4 Fig</a> <b>PA</b>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180419#pone.0180419.s006" target="_blank">S5 Fig</a> <b>M</b>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180419#pone.0180419.s007" target="_blank">S6 Fig</a> <b>NP</b>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180419#pone.0180419.s008" target="_blank">S7 Fig</a> <b>NS</b>). Colours for seasons: RED, 2009–2010; BRIGHT GREEN, 2010–2011; PURPLE, 2011–2012; BLUE SKY, 2012–2013; VIOLET, 2013–2014.</p