Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis

Abstract

Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies.

Sphingolipid Pathway as a Source of Vulnerability in IDH1mut Glioma

“…Pooled quality control (QC) samples were composed with 10% volume of each sample. Lipids were resolved using Acquity UPLC CSH 1.7 µm, 2.1 × 100 mm column (Waters Corp. Milford, MA, USA) with a gradient described previously [ 22 , 30 ].…”

Role of downregulated ADARB1 in lung squamous cell carcinoma

“…additionally, using next-generation sequencing transcriptomics, chan et al (40) reported that ADARB1 contributed to inhibitory mechanisms in gastric cancer via its catalytic deaminase. However, altadill et al (41) demonstrated that ADARB1 was upregulated in endometrial cancer, and the increased expression was positively associated with disease aggression, suggesting that ADARB1 functions as an oncogene in endometrial cancer. The inconsistency between the observations of these aforementioned studies and the present study may be due to the diverse pathological states of different diseases; therefore, further investigation is required.…”

Systematic Construction and Validation of an RNA Binding Proteins-Based Signature for Prognostic Prediction in Gastric Cancer

“…BOLL functions as an oncogene because of enhancing proliferation and migration activities in the colon cancer cells, and BOLL protein expression was upregulated in colorectal cancer tissue [36]. ADARB1 was expressed at high levels in endometrial cancer, and observed a positive correlation between increased expression and invasion degree [37]. Another study reported that ADARB1 could inhibit glioblastoma cell growth via regulation of the CDC14B/Skp2/p21/p27 axis [38].…”