Navigating The CeRNA Axis by Bioinformatics and Experimental Validation: Identification of ADIRF-AS1, miR-191-5p, and EGR1 as Key Players in Endometrial Carcinoma Progression.
Azadeh Rezaei, Rahim Rostami, Shahram Teimourian, Saman Morovat, Elmira Mehdinia, Afsaneh Tehranian, Soudabeh Fallah
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引用次数: 0
Abstract
Background: Endometrial carcinoma (EC) is a significant gynecologic malignancy. Investigating competing endogenous RNA (ceRNA) networks, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs), offers insights into EC's molecular intricacies and may improve therapeutic and diagnostic strategies. This study focuses on the ceRNA axis, particularly the interactions of lncRNA-miRNA-mRNA-Gene, using TCGA-UCEC database analysis and experimental validation.
Materials and methods: In this case-control study, differentially expressed lncRNAs (DElncRNAs), microRNAs (DEMIs), and genes (DEGs) were identified, highlighting ADIRF-AS1 as a potential target. Validated interactions between ADIRF-AS1, miR-191-5p, and EGR1 were established, with significant ADIRF-AS1/EGR1 correlation. Protein-protein interaction (PPI) analysis identified 21 proteins linked to EGR1, with gene ontology (GO) analysis revealing roles in myeloid cell differentiation. Expression levels of genes, lncRNA, and microRNAs were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blot analysis was applied for protein evaluation.
Results: RT-qPCR results showed that the RNA expression levels of ADIRF-AS1 and EGR1 genes in endometrial cancer and hyperplasia samples were significantly lower (P<0.001) than control samples. Also, the expression level of miR-191-5p in endometrial cancer tissues was significantly higher than patients with hyperplasia (P<0.001) and normal samples (P<0.001). Western blot results also showed that the protein level of EGR1 in endometrial cancer samples was significantly lower than control samples (P<0.001).
Conclusion: Here, we observed an interaction between lncRNA ADIRF-AS1and hsa-miR-191-5p, and also, ADIRFAS1 downstream effects on EGR1 in EC, that seems may be a suggesting therapeutic and diagnostic targets. Further research could explore its clinical relevance in endometrial carcinoma.
期刊介绍：
International Journal of Fertility & Sterility is a quarterly English publication of Royan Institute . The aim of the journal is to disseminate information through publishing the most recent scientific research studies on Fertility and Sterility and other related topics. Int J Fertil Steril has been certified by Ministry of Culture and Islamic Guidance in 2007 and was accredited as a scientific and research journal by HBI (Health and Biomedical Information) Journal Accreditation Commission in 2008. Int J Fertil Steril is an Open Access journal.
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