Identification of an eight-m6A RNA methylation regulator prognostic signature of uterine corpus endometrial carcinoma based on bioinformatics analysis

Miao, Chenyun; Fang, Xiaojie; Chen, Yun; Zhao, Ying; Guo, Qingge

doi:10.1097/md.0000000000027689

Cited by 6 publications

(3 citation statements)

References 34 publications

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“…However, these studies used different study design, sampling method, statistical measures, and validation approaches. Even though the number of publications aimed at studying the effect of miRNAs is increasing, understanding of miRNAs role in the carcinogenesis process and their effect on gene expression is lacking ( He et al, 2015 ; Liu Y et al, 2020 ; Miao et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Computational approaches for discovering significant microRNAs, microRNA-mRNA regulatory pathways, and therapeutic protein targets in endometrial cancer

Ajabnoor

Alsubhi²,

Shinawi³

et al. 2023

Front. Genet.

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Endometrial cancer (EC) is a urogenital cancer affecting millions of post-menopausal women, globally. This study aims to identify key miRNAs, target genes, and drug targets associated with EC metastasis. The global miRNA and mRNA expression datasets of endometrial tissue biopsies (24 tumors +3 healthy tissues for mRNA and 18 tumor +4 healthy tissues for miRNAs), were extensively analyzed by mapping of DEGs, DEMi, biological pathway enrichment, miRNA-mRNA networking, drug target identification, and survival curve output for differentially expressed genes. Our results reveal the dysregulated expression of 26 miRNAs and their 66 target genes involved in focal adhesions, p53 signaling pathway, ECM-receptor interaction, Hedgehog signaling pathway, fat digestion and absorption, glioma as well as retinol metabolism involved in cell growth, migration, and proliferation of endometrial cancer cells. The subsequent miRNA-mRNA network and expression status analysis have narrowed down to 2 hub miRNAs (hsa-mir-200a, hsa-mir-429) and 6 hub genes (PTCH1, FOSB, PDGFRA, CCND2, ABL1, ALDH1A1). Further investigations with different systems biology methods have prioritized ALDH1A1, ABL1 and CCND2 as potential genes involved in endometrial cancer metastasis owing to their high mutation load and expression status. Interestingly, overexpression of PTCH1, ABL1 and FOSB genes are reported to be associated with a low survival rate among cancer patients. The upregulated hsa-mir-200a-b is associated with the decreased expression of the PTCH1, CCND2, PDGFRA, FOSB and ABL1 genes in endometrial cancer tissue while hsa-mir-429 is correlated with the decreased expression of the ALDH1A1 gene, besides some antibodies, PROTACs and inhibitory molecules. In conclusion, this study identified key miRNAs (hsa-mir-200a, hsa-mir-429) and target genes ALDH1A1, ABL1 and CCND2 as potential biomarkers for metastatic endometrial cancers from large-scale gene expression data using systems biology approaches.

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Section: Discussionmentioning

confidence: 99%

Computational approaches for discovering significant microRNAs, microRNA-mRNA regulatory pathways, and therapeutic protein targets in endometrial cancer

Ajabnoor

Alsubhi²,

Shinawi³

et al. 2023

Front. Genet.

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“…In addition, there are two mRNA-miRNA regulatory axes, i.e., (mRNA LRPPRC)-(miRNA hsa-miR-4658) and (mRNA LRPPRC)-(miRNA hsa-miR-6783-5p). Study by [23] constructed a prognostic model and nomogram for UCEC based on eight m6A regulatory factors, including LRPPRC, suggesting that LRPPRC plays a significant role in UCEC. However, the three miRNA targets were not reported to be UCEC-related in previous studies.…”

Section: Discussionmentioning

confidence: 99%

Identifying the Role of Disulfidptosis in Endometrial Cancer via Machine Learning Methods

Fu,

Lu,

Zhang

et al. 2023

BioMedInformatics

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Uterine corpus endometrial carcinoma (UCEC) is the second most common gynecological cancer in the world. With the increased occurrence of UCEC and the stagnation of research in the field, there is a pressing need to identify novel UCEC biomarkers. Disulfidptosis is a novel form of cell death, but its role in UCEC is unclear. We integrate differential analysis and the XGBoost algorithm to determine a disulfidptosis-related characteristic gene (DRCG), namely LRPPRC. By prediction and verification based on online databases, we construct a regulatory network of ceRNA in line with the scientific hypothesis, including a ceRNA regulatory axis and two mRNA-miRNA regulatory axes, i.e., mRNA LRPPRC/miRNA hsa-miR-616-5p/lncRNA TSPEAR-AS2, mRNA LRPPRC/miRNA hsa-miR-4658, and mRNA LRPPRC/miRNA hsa-miR-6783-5p. We use machine learning methods such as GBM to screen out seven disulfidptosis-related characteristic lncRNAs (DRCLs) as predictors, and build a risk prediction model with good prediction ability. SCORE = (1.136*LINC02449) + (−2.173*KIF9-AS1) + (−0.235*ACBD3-AS1) + (1.830*AL354892.3) + (−1.314*AC093677.2) + (0.636*AC113361.1) + (−0.589*CDC37L1-DT). The ROC curve shows that in the training set samples, the AUCs for predicting 1-, 3-, 6-, and 10-year OS are 0.804, 0.724, 0.719, and 0.846, respectively. In the test set samples, the AUCs for predicting 1-, 3-, 6-, and 10-year OS are 0.615, 0.657, 0.687, and 0.702, respectively. In all samples, the AUCs for predicting 1-, 3-, 6-, and 10-year OS are 0.752, 0.706, 0.705, and 0.834, respectively. CP724714 has been screened as a potential therapy option for individuals who have a high risk of developing UCEC. Two subtypes of disulfidptosis-related genes (DRGs) and two subtypes of DRCLs are obtained by NMF method. We find that subtype N1 of DRGs is mainly enriched in various metabolic pathways, and subtype N1 may play a significant role in the process of disulfidptosis. Our study confirms for the first time that disulfidptosis plays a role in UCEC. Our findings help improve the prognosis and treatment of UCEC.

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“…Wang et al outline new insights into CNVs/SNVs in m6A regulatory genes which were associated with a negative impact on patient survival of EC and ultimately found that three genes, IGF2BP3, KIAA1429, and IGF2BP1 , were effective predictors of EC outcomes ( Wang et al, 2020 ). Similarly, Chen et al selected the risk signature of 8-m6A regulators as the potential predictive prognostic value for EC ( Miao et al, 2021 ).…”

Section: Network Resourcesmentioning

confidence: 99%

Shining a spotlight on m6A and the vital role of RNA modification in endometrial cancer: a review

Jin,

Sheng,

et al. 2023

Front. Genet.

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RNA modifications are mostly dynamically reversible post-transcriptional modifications, of which m6A is the most prevalent in eukaryotic mRNAs. A growing number of studies indicate that RNA modification can finely tune gene expression and modulate RNA metabolic homeostasis, which in turn affects the self-renewal, proliferation, apoptosis, migration, and invasion of tumor cells. Endometrial carcinoma (EC) is the most common gynecologic tumor in developed countries. Although it can be diagnosed early in the onset and have a preferable prognosis, some cases might develop and become metastatic or recurrent, with a worse prognosis. Fortunately, immunotherapy and targeted therapy are promising methods of treating endometrial cancer patients. Gene modifications may also contribute to these treatments, as is especially the case with recent developments of new targeted therapeutic genes and diagnostic biomarkers for EC, even though current findings on the relationship between RNA modification and EC are still very limited, especially m6A. For example, what is the elaborate mechanism by which RNA modification affects EC progression? Taking m6A modification as an example, what is the conversion mode of methylation and demethylation for RNAs, and how to achieve selective recognition of specific RNA? Understanding how they cope with various stimuli as part of in vivo and in vitro biological development, disease or tumor occurrence and development, and other processes is valuable and RNA modifications provide a distinctive insight into genetic information. The roles of these processes in coping with various stimuli, biological development, disease, or tumor development in vivo and in vitro are self-evident and may become a new direction for cancer in the future. In this review, we summarize the category, characteristics, and therapeutic precis of RNA modification, m6A in particular, with the purpose of seeking the systematic regulation axis related to RNA modification to provide a better solution for the treatment of EC.

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Identification of an eight-m6A RNA methylation regulator prognostic signature of uterine corpus endometrial carcinoma based on bioinformatics analysis

Cited by 6 publications

References 34 publications

Computational approaches for discovering significant microRNAs, microRNA-mRNA regulatory pathways, and therapeutic protein targets in endometrial cancer

Computational approaches for discovering significant microRNAs, microRNA-mRNA regulatory pathways, and therapeutic protein targets in endometrial cancer

Identifying the Role of Disulfidptosis in Endometrial Cancer via Machine Learning Methods

Shining a spotlight on m6A and the vital role of RNA modification in endometrial cancer: a review

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