Small non-coding RNA deregulation in endometrial carcinogenesis

Abstract

Small non-coding RNAs (sncRNAs) represent a heterogeneous group of <200nt-long transcripts comprising microRNAs, PIWI-interacting RNAs (piRNAs) and small-nucleolar-RNAs (snoRNAs) involved in physiological and pathological processes such as carcinogenesis and tumor progression. Aberrant sncRNA expression in cancer has been associated with specific clinical phenotypes, grading, staging, metastases development and resistance to therapy.Aim of the present work is to study the role of sncRNAs in endometrial carcinogenesis. Changes in sncRNA expression were identified by high-throughput genomic analysis of paired normal, hyperplastic and cancerous endometrial tissues obtained by endometrial biopsies (n = 10). Using smallRNA sequencing and microarrays we identified significant differences in sncRNA expression pattern between normal, hyperplastic and neoplastic endometrium. This led to the definition of a sncRNA signature (129 microRNAs, 2 of which not previously described, 10 piRNAs and 3 snoRNAs) of neoplastic transformation. Functional bioinformatics analysis identified as downstream targets multiple signaling pathways potentially involved in the hyperplastic and neoplastic tissue responses, including Wnt/β-catenin, and ERK/MAPK and TGF-β-Signaling.Considering the regulatory role of sncRNAs, this newly identified sncRNA signature is likely to reflect the events leading to endometrial cancer, which can be exploited to dissect the carcinogenic process including novel biomarkers for early and non-invasive diagnosis of these tumors.

miRNA Regulation of the Hyperproliferative Phenotype of Vascular Smooth Muscle Cells in Diabetes

“…At 2 days after injury, total RNA was extracted from carotid arteries in each group and processed for RNA-Seq as previously described (19)(20)(21)(22)(23). Indexed libraries were prepared from 600 ng/each purified RNA pool with TruSeq Stranded Total RNA Sample Prep Kit (Illumina).…”

Dioscin protects against coronary heart disease by reducing oxidative stress and inflammation via Sirt1/Nrf2 and p38 MAPK pathways

“…p38 mitogen-activated protein kinase (MAPK) is a type of tyrosine/threonine protein kinase with a molecular weight of ~40-60 kDa; all members of the MAPK family are activated by dual phosphorylation of tyrosine and threonine (17). Tyrosine kinase receptors, G-protein-coupled receptors and ion channel-coupled receptors may initiate the phosphorylation of tyrosine and threonine sites on MAPKs through various intermediary links to activate p38 MAPK, and activated p38 MAPK subsequently translocates to its corresponding transcription factors and activates gene transcription, resulting in effects on cell proliferation, growth or apoptosis (17,18). p38 MAPK is considered to be the focal point or common pathway of the transmission of various extracellular signals that lead to cell proliferation, hypertrophy and apoptosis, and participates in myocardial hypertrophy, proliferation and apoptosis induced by a various stimuli (19).…”

Understanding Molecular Landscape of Endometrial Cancer through Next Generation Sequencing: What We Have Learned so Far?

“…A genome wide characterization of small non-coding RNAs (sncRNAs) in EC carcinogenesis was performed on biopsies of normal ( n = 10), hyperplastic ( n = 6) and tumor Type 1 endometrial tissues ( n = 10) using RNA sequencing (Ravo et al, 2015). Significant patterns in sncRNA expression between the sample groups were identified and led to the discovery of sncRNAs signature (129 miRNAs, 10 piRNAs, and three snoRNAs) which is said to be involved in neoplastic transformation (Ravo et al, 2015).…”

“…Significant patterns in sncRNA expression between the sample groups were identified and led to the discovery of sncRNAs signature (129 miRNAs, 10 piRNAs, and three snoRNAs) which is said to be involved in neoplastic transformation (Ravo et al, 2015). Integrated gene expression profiling with the aberrantly expressed sncRNAs signature revealed their involvement in multiple signaling pathway including ERK/MAPK, TGF-β and Wnt/β-catenin in both hyperplastic and neoplastic tissues (Ravo et al, 2015). …”