12 research outputs found
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