Dataset Information

Involving the microRNA Targetome in Esophageal-Cancer Development and Behavior.

ABSTRACT: Esophageal cancer (EC) is the eighth most common and sixth leading cause of cancer-related mortality in the world. Despite breakthroughs in EC diagnosis and treatment, patients with complete pathologic response after being submitted to chemoradiotherapy are still submitted to surgery, despite its high morbidity. Single-nucleotide polymorphisms (SNPs) in miRNA, miRNA-binding sites, and in its biogenesis pathway genes can alter miRNA expression patterns, thereby influencing cancer risk and prognosis. In this review, we systematized the information available regarding the impact of these miR-SNPs in EC development and prognosis. We found 34 miR-SNPs that were associated with EC risk. Despite the promising applicability of these miR-SNPs as disease biomarkers, they still lack validation in non-Asian populations. Moreover, there should be more pathway-based approaches to evaluate the cumulative effect of multiple unfavorable genotypes and, consequently, identify miR-SNPs signatures capable of predicting EC therapy response and prognosis.

SUBMITTER: Dias F

PROVIDER: S-EPMC6210990 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Involving the microRNA Targetome in Esophageal-Cancer Development and Behavior.

Dias Francisca F Morais Mariana M Teixeira Ana Luísa AL Medeiros Rui R

Cancers 20181012 10

Esophageal cancer (EC) is the eighth most common and sixth leading cause of cancer-related mortality in the world. Despite breakthroughs in EC diagnosis and treatment, patients with complete pathologic response after being submitted to chemoradiotherapy are still submitted to surgery, despite its high morbidity. Single-nucleotide polymorphisms (SNPs) in miRNA, miRNA-binding sites, and in its biogenesis pathway genes can alter miRNA expression patterns, thereby influencing cancer risk and prognos ...[more]

PMID: 30322005

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Project description:BackgroundEsophageal cancer (ESCA) is a heterogeneous cancer with variable outcomes that are challenging to predict. MicroRNA (miR)-1269a is a newly discovered non-coding RNA that shows promising prognostic prediction in other cancers, but its clinical value in ESCA remains unclear.AimTo explore the relationship between miR-1269a and its clinical value and to develop a nomogram to succinctly display this relationship.MethodsWe analyzed the expression of miR-1269a in 125 ESCA tissue samples with complete clinical data and 52 normal tissue samples. We determined the prognostic value of miR-1269a for overall survival (OS) and cancer-specific survival (CSS) and evaluated the association between miR-1269a and clinical variables including tumor location, histologic grade, metastatic stage, and American Joint Committee on Cancer (AJCC) stage using multivariate Cox analysis. Additionally, we developed a nomogram for OS and CSS based on miR-1269a expression using age and AJCC stage and assessed its prognostic performance. Using Gene Ontology and Kyoto Encyclopedia of Gene and Genomes analyses, we predicted the target genes of miR-1269a and analyzed their potential function in caner development.ResultsThe expression of miR-1269a was significantly higher in ESCA patients than healthy controls. Patients with high expression of miR-1269a showed poor prognosis in OS and CSS, suffered increased rates of low differentiation and metastasis, and exhibited tumor stage T3 + T4, positive lymph stage, and AJCC stage III + IV. The area under the receiver operating characteristic curve of miR-1269a was 0.716 for OS and 0.764 for CSS. Multivariate Cox analysis revealed that AJCC stage and miR-1269a were independent factors for OS and CSS. Combing with age, we constructed a nomogram for prognostic prediction. Additionally, our nomogram showed excellent predictive performance for OS and CSS after 3 years and 5 years and was easy to use. Ultimately, the functional analysis suggested that miR-1269a was mostly involved in the PI3K-AKT signaling pathway.ConclusionmiR-1269a can be used as a potential indicator for the prognosis of ESCA patients. We developed an easy-to-use nomogram with excellent ESCA prognostic prediction for clinical use.

Project description:BackgroundMicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases including age-related macular degeneration (AMD), acting as post-transcriptional gene suppressors through their association with argonaute 2 (AGO2) - a key member of the RNA Induced Silencing Complex (RISC). Identifying the retinal miRNA/mRNA interactions in health and disease will provide important insight into the key pathways miRNA regulate in disease pathogenesis and may lead to potential therapeutic targets to mediate retinal degeneration.MethodsTo identify the active miRnome targetome interactions in the healthy and degenerating retina, AGO2 HITS-CLIP was performed using a rodent model of photoreceptor degeneration. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data was performed to identify the cellular location of AGO2 and key members of the microRNA targetome in the retina. AGO2 findings were verified by in situ hybridization (RNA) and immunohistochemistry (protein).ResultsAnalysis revealed a similar miRnome between healthy and damaged retinas, however, a shift in the active targetome was observed with an enrichment of miRNA involvement in inflammatory pathways. This shift was further demonstrated by a change in the seed binding regions of miR-124-3p, the most abundant retinal AGO2-bound miRNA, and has known roles in regulating retinal inflammation. Additionally, photoreceptor cluster miR-183/96/182 were all among the most highly abundant miRNA bound to AGO2. Following damage, AGO2 expression was localized to the inner retinal layers and more in the OLM than in healthy retinas, indicating a locational miRNA response to retinal damage.ConclusionsThis study provides important insight into the alteration of miRNA regulatory activity that occurs as a response to retinal degeneration and explores the miRNA-mRNA targetome as a consequence of retinal degenerations. Further characterisation of these miRNA/mRNA interactions in the context of the degenerating retina may provide an important insight into the active role these miRNA may play in diseases such as AMD.

Dataset Information

Involving the microRNA Targetome in Esophageal-Cancer Development and Behavior.

Publications

Involving the microRNA Targetome in Esophageal-Cancer Development and Behavior.

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