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Although a large part of the genome is transcribed, only 1.9% has a protein-coding potential; most of the transcripts are non-coding RNAs such as snRNAs, tRNAs, and rRNAs that participate in mRNA processing and translation. In addition, there are small RNAs with a regulatory role, such as siRNAs, miRNAs, and piRNAs. Finally, the long non-coding RNAs (lncRNAs) are transcripts of more than 200 bp that can positively and negatively regulate gene expression (both in cis and trans), serve as a scaffold for protein recruitment, and control nuclear architecture, among other functions. An essential process regulated by lncRNAs is genome stability. LncRNAs regulate genes associated with DNA repair and chromosome segregation; they are also directly involved in the maintenance of telomeres and have recently been associated with the activity of the centromeres. In cancer, many alterations in lncRNAs have been found to promote genomic instability, which is a hallmark of cancer and is associated with resistance to chemotherapy. In this review, we analyze the most recent findings of lncRNA alterations in cancer, their relevance in genomic instability, and their impact on the resistance of tumor cells to anticancer therapy.

Prostate cancer is the most common cancer in men and the second leading cause of cancer-related deaths. The most used biomarker to detect prostate cancer is Prostate Specific Antigen (PSA), whose levels are measured in serum. However, it has been recently established that molecular markers of cancer should not be based solely on genes and proteins but should also reflect other genomic traits; long non-coding RNAs (lncRNAs) serve this purpose. lncRNAs are transcripts of >200 bases that do not encode proteins and that have been shown to display abnormal expression profiles in different types of cancer. Experimental studies have highlighted lncRNAs as potential biomarkers for prognoses and treatments in patients with different types of cancer, including prostate cancer, where the PCA3 lncRNA is currently used as a diagnostic tool and management strategy. With the development of genomic technologies, particularly next-generation sequencing (NGS), several other lncRNAs have been linked to prostate cancer and are currently under validation for their medical use. In this review, we will discuss different strategies for the discovery of novel lncRNAs that can be evaluated as prognostic biomarkers, the clinical impact of these lncRNAs and how lncRNAs can be used as potential therapeutic targets.

Background Inhaled nanoparticles (NPs) challenges mobile and immobile barriers in the respiratory tract, which can be represented by type II pneumocytes (immobile) and monocytes (mobile) but what is more important for biological effects, the cell linage, or the type of nanoparticle? Here, we addressed these questions and we demonstrated that the type of NPs exerts a higher influence on biological effects, but cell linages also respond differently against similar type of NPs. Design. Type II pneumocytes and monocytes were exposed to tin dioxide (SnO2) NPs and titanium dioxide (TiO2) NPs (1, 10 and 50 μg/cm2) for 24 h and cell viability, ultrastructure, cell granularity, molecular spectra of lipids, proteins and nucleic acids and cytoskeleton architecture were evaluated. Results. SnO2 NPs and TiO2 NPs are metal oxides with similar physicochemical properties. However, in the absence of cytotoxicity, SnO2 NPs uptake was low in monocytes and higher in type II pneumocytes, while TiO2 NPs were highly internalized by both types of cells. Monocytes exposed to both types of NPs displayed higher number of alterations in the molecular patterns of proteins and nuclei acids analyzed by Fourier-transform infrared spectroscopy (FTIR) than type II pneumocytes. In addition, cells exposed to TiO2 NPs showed more displacements in FTIR spectra of biomolecules than cells exposed to SnO2 NPs. Regarding cell architecture, microtubules were stable in type II pneumocytes exposed to both types of NPs but actin filaments displayed a higher number of alterations in type II pneumocytes and monocytes exposed to SnO2 NPs and TiO2 NPs. NPs exposure induced the formation of large vacuoles only in monocytes, which were not seen in type II pneumocytes. Conclusions. Most of the cellular effects are influenced by the NPs exposure rather than by the cell type. However, mobile, and immobile barriers in the respiratory tract displayed differential response against SnO2 NPs and TiO2 NPs in absence of cytotoxicity, in which monocytes were more susceptible than type II pneumocytes to NPs exposure.

The telomere protects against genomic instability by minimizing the accelerated end resection of the genetic material, a phenomenon that results in severe chromosome instability that could favor the transformation of a cell by enabling the emergence of tumor-promoting mutations. Some mechanisms that avoid this fate, such as capping and loop formation, have been very well characterized; however, telomeric non-coding transcripts, such as long non-coding RNAs (lncRNAs), should also be considered in this context because they play roles in the organization of telomere dynamics, involving processes such as replication, degradation, extension, and heterochromatin stabilization. Although the mechanism through which the expression of telomeric transcripts regulates telomere dynamics is not yet clear, a non-coding RNA component opens the research options in telomere biology and the impact that it can have on telomere-associated diseases such as cancer.

In this review several characteristics of the aging process are described and some theories that try to explain it are briefly mentioned. Although none of them fully explains this phenomenon, they can interact between each other in a complex way, out of which cellular senescence is the common outcome. Molecular changes take place on both genetic and epigenetic levels, and several studies have associated senescence with changes in the epigenetic-mediated chromatin condensation, while others consider that free radicals represent a useful mechanism to explain aging and age-related disorders that, along with the alteration of mitochondrial homeostasis, promote the aging process through the accumulation of damage along time.En esta revisión se describen varias características del proceso de envejecimiento y de manera resumida algunas de las teorías que intentan explicarlo y, si bien ninguna es totalmente satisfactoria, pueden actuar entre sí de una manera compleja; en ellas, la senescencia celular es el factor común. Las alteraciones moleculares se llevan a cabo tanto a nivel genético como epigenético y varios estudios asocian la senescencia con cambios en la condensación de la cromatina, los cuales están regulados por factores epigenéticos y otros; en esos estudios se considera que los radicales libres representan un mecanismo útil para explicar el envejecimiento y los trastornos relacionados con la edad y que en forma conjunta, con las alteraciones en la homeostasis de la mitocondria, promueven el envejecimiento por daño acumulado a través del tiempo.

MicroRNAs are small non-coding ribonucleic acids of endogenous nature. They persist in various groups of eukaryotes and perform critical functions during the development and the cell homeostasis. They have from 19 to 25 nucleotides in length and regulate the translation of the target RNA messenger (mRNA). MicroRNAs can inhibit its translation, stabilizing it or inducing its degradation. They regulate the genetic expression and are involved in the control of cellular functions (the differentiation, the proliferation, the apoptosis and the metabolism). They are also involved in the response to stress, the angiogenesis, the oncogenesis and in cardiovascular functions. That is the reason why their abnormal expressions are associated to many pathological conditions. The aim of this review was to describe the importance of microRNAs, their biological origin and their role in various diseases, such as cancer, diabetes, obesity, and neurological disorders. The microRNAs are an attractive therapeutic target because it has been observed that just one of them can regulate several genes and it could influence all the signaling route; besides, they could inhibit themselves in vivo without adverse effects related to the usual therapeutic agents. Since they can be detected in serum, plasma, urine and saliva samples in a stable, reproducible and consistent form between individuals of the same species, we expect them to be useful as biomarkers for the clinical diagnosis and the monitoring of diseases.Los microARN son ácidos ribonucleicos pequeños no codificantes, endógenos, que se encuentran conservados en varios grupos de eucariontes y que desempeñan funciones críticas durante el desarrollo y la homeostasis celular. Son secuencias de una longitud entre 19 y 25 nucleótidos, que regulan la traducción de un ARN mensajero (ARNm) blanco, que inhiben su traducción, estabilizándolo o llevándolo a su degradación. Los microARN son reguladores de la expresión génica y participan en el control de procesos celulares como la diferenciación, la proliferación, la apoptosis y el metabolismo; también están involucrados en la respuesta al estrés, en la angiogénesis, la oncogénesis y los procesos cardiovasculares. De ahí que su desregulación o expresión anormal esté relacionada con numerosas condiciones patológicas. Esta revisión describe la importancia de los microARN, su biogénesis y su participación en enfermedades como cáncer, diabetes, obesidad y trastornos neurológicos. Los microARN representan un atractivo blanco terapéutico porque se ha observado que uno solo puede regular a muchos genes blanco e influir en toda la vía de señalización; además, pueden inhibirse in vivo sin muchos de los efectos adversos relacionados con los agentes terapéuticos tradicionales. Dado que se pueden detectar en suero, plasma, orina y saliva en forma estable, reproducible y consistente entre individuos de la misma especie, se espera que puedan utilizarse como biomarcadores para el diagnóstico clínico y monitoreo de enfermedades.

Telomere length is regulated by epigenetic marks that modulate, among other things, the expression of the telomerase catalytic subunit. Telomeres and sub-telomeric regions are enriched in histone marks associated to constitutive heterochromatin. The marks before mentioned are essential for the maintenance of telomere integrity and therefore for genomic stability, but there is another kind of regulation that depends on ncRNAs. This is the case of the lncRNA Telomere repeat-containing RNA (TERRA), an element required for telomeric integrity, considered to hinder chromosomal instability where anaphase bridges, sister chromatid fusions and multi-telomeric regions can take place. This instability leads to chromosomal aberrations that could produce a malignant cell lineage, however, in order for this event to take place, a telomere healing process must occur so that the ribonucleoproteic complex of the telomere can be stabilized once more. For this reason it is important to study the role that the lncRNA TERRA plays in telomere stabilization and how its malfunctioning can bring forth an carcinogenic process. The telomeric regions of interest were analyzed using the data base of the University of California in Santa Cruz (UCSC). We chose the short arm of chromosome 5, where telomerase is encoded, and looked for elements associated to promoter regions such as the presence of the nuclear factor CTCF, Polymerase II, histone marks related with promoters (H3K4me3 and H3K4me1), potential transcription start sites (TSS) and sequences with enhancer potential. We worked with two cell lines of the same cell lineage K562 and SC, in order to have a leukemic and a non-transformed cell model. In order to enrich the amount of TERRA after RNA extraction, we synthesized cDNA using both dT primers and telomere repeat-containing oligonucleotides. The cDNA was used to evaluate the total amount of TERRA in both cell lines using the expression of the ncRNAs U6, HOTAIR and H19 as an amplification reference. We demonstrated that the short arm of chromosome 5 does codify for TERRA, and we verified that only the DNA strand that encodes TERRA was transcribed. Furthermore, we confirmed that the predicted TSS was functional. qPCR showed that there are changes in TERRA expression that take place in accordance with population doubling events. This was observed in the analyzed telomeres of both cell lines used. These results could be related with the natural shortening of telomeres that happens in non-transformed cells, but since such a process is absent in leukemic cells, further investigation is required to answer this query. Citation Format: Diego A. Oliva-Rico, Rodrigo Gonzalez-Barrios, Eunice Fabian-Morales, Luis A. Herrera. Regulation of the telomere healing process by the lncRNA TERRA. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 542. doi:10.1158/1538-7445.AM2014-542