Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression

Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC

Identification of serotoninergic system components in stallion sperm

Assisted reproductive techniques have been used on several domestic animals to preserve desirable traits in strains of high genetic and commercial value; however in equines its efficiency rate is relatively low. To increase the conception ratio in stallions, some research groups have used pharmacological treatments which promote sperm hyperactivation in order to increase male’s fertility rates. In this way, our previous work suggests that serotonin (5-HT) could be a good pharmacological candidate that facilitates conception rate in domestic horses. 5-HT is a neurohormone involved in several reproductive processes, i.e., it enhances hyperactivation, motility, and promotes the acrosome reaction in mammalian sperm, but it has not been described in the stallion sperm yet. Therefore, using both immunofluorescence and western blot techniques, we searched for and found some serotonin markers such as 5-HT, 5-HT1B, 5-HT2A, 5-HT3 receptors, both TPH1 and MAOA enzymes, and serotonin transporter (5-HTT) in stallion sperm. In addition, we found a non-neuroendocrine cell, V-MAT1 transporter, which has not been previously reported in mammalian sperm. Our results suggest that serotoninergic system is present in stallion sperm, which could be a pharmacological target to increase the conception rates in domestic horses

Transcriptional profiles reveal deregulation of lipid metabolism and inflammatory pathways in neurons exposed to palmitic acid.

The effects of the consumption of high-fat diets (HFD) have been studied to unravel the molecular pathways they are altering in order to understand the link between increased caloric intake, metabolic diseases, and the risk of cognitive dysfunction. The saturated fatty acid, palmitic acid (PA), is the main component of HFD and it has been found increased in the circulation of obese and diabetic people. In the central nervous system, PA has been associated with inflammatory responses in astrocytes, but the effects on neurons exposed to it have not been largely investigated. Given that PA affects a variety of metabolic pathways, we aimed to analyze the transcriptomic profile activated by this fatty acid to shed light on the mechanisms of neuronal dysfunction. In the current study, we profiled the transcriptome response after PA exposition at non-toxic doses in primary hippocampal neurons. Gene ontology and Reactome pathway analysis revealed a pattern of gene expression which is associated with inflammatory pathways, and importantly, with the activation of lipid metabolism that is considered not very active in neurons. Validation by quantitative RT-PCR (qRT-PCR) of Hmgcs2, Angptl4, Ugt8, and Rnf145 support the results obtained by RNAseq. Overall, these findings suggest that neurons are able to respond to saturated fatty acids changing the expression pattern of genes associated with inflammatory response and lipid utilization that may be involved in the neuronal damage associated with metabolic diseases

The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics

MicroRNAs are small noncoding transcripts that posttranscriptionally regulate gene expression via base-pairing complementarity. Their role in cancer can be related to tumor suppression or oncogenic function. Moreover, they have been linked to processes recognized as hallmarks of cancer, such as apoptosis, invasion, metastasis, and proliferation. Particularly, one of the first oncomiRs found upregulated in a variety of cancers, such as gliomas, breast cancer, and colorectal cancer, was microRNA-21 (miR-21). Some of its target genes associated with cancer are PTEN (phosphatase and tensin homolog), PDCD4 (programmed cell death protein 4), RECK (reversion-inducing cysteine-rich protein with Kazal motifs), and STAT3 (signal transducer activator of transcription 3). As a result, miR-21 has been proposed as a plausible diagnostic and prognostic biomarker, as well as a therapeutic target for several types of cancer. Currently, research and clinical trials to inhibit miR-21 through anti-miR-21 oligonucleotides and ADM-21 are being conducted. As all of the evidence suggests, miR-21 is involved in carcinogenic processes; therefore, inhibiting it could have effects on more than one type of cancer. However, whether miR-21 can be used as a tissue-specific biomarker should be analyzed with caution. Consequently, the purpose of this review is to outline the available information and recent advances regarding miR-21 as a potential biomarker in the clinical setting and as a therapeutic target in cancer to highlight its importance in the era of precision medicine