CircRNA-miRNA-mRNA interactome analysis in endometrial cancer

Tikam Chand Dakal, Abhishek Kumar, Pawan Kumar Maurya
Journal of biomolecular structure & dynamics · 2025 · vol. 43(3) , pp. 1486–1497 · doi:10.1080/07391102.2023.2291834 · PMID:38084757
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⚙ AI-generated summary by claude@2026-06, 2026-06-10 ⓘ

This study constructed a circRNA-miRNA-mRNA network to identify potential diagnostic and therapeutic targets in endometrial cancer, revealing novel candidate genes and miRNAs.

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The study analyzed a circRNA–miRNA–mRNA interactome to identify molecular processes and pathways associated with endometrial cancer, using two endometrial cancer–associated circRNAs (hsa_circ_0002577 and hsa_circ_0109046) retrieved from circad. It predicted miRNA sponging sites on these circRNAs and then predicted target mRNAs for the associated miRNAs, implicating oncogenes, tumor suppressors, autophagy and apoptosis regulators, transcription factors, growth factors, and other gene candidates in the regulatory network; hsa-miR-433-3p was reported to have significant predictive relevance for assessing patient response to chemotherapy (fold change 1.8, AUC 0.736, Mann–Whitney p = 6.1e-14). A limitation stated in the abstract is that the interactome describes putative molecular associations based on prediction rather than direct experimental validation, and the approach highlights novel candidates not previously implicated in endometrial cancer. Relevance to endometriosis: the abstract explicitly mentions that hsa-miR-188-3p is upregulated in endometriosis, though the paper’s main focus is endometrial cancer circRNA–miRNA–mRNA network analysis.

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Abstract

In recent years, exploring the potential of miRNAs as novel diagnostic, prognostic and diagnostic markers have gained much attention. In current study, we conducted an in-depth circRNA-miRNA-mRNA interactome to reveal significant molecular processes and biological pathways putatively associated with endometrial cancer (EC). Firstly, we retrieved two circRNAs from circad, hsa_circ_0002577 & hsa_circ_0109046, based on their association with the EC. Subsequently, we predicted miRNAs sponging sites in the two circRNAs and the potential target mRNAs of the predicted miRNAs. Sequestered miRNAs target a number of oncogenes (CBL, MET, KRAS), tumor suppressor (CFT R), receptor protein kinases & GT Pase (MET, KRAS, RAB1B), methyltransferases (SET D8), receptors associated factors (T RAF2, GRB2), growth factors (FGF20), autophagy (BECN1, AT G14), apoptotic regulators (BCL2), transcription factors (T Fs) (CREB1, RUNX1, RUNX2) and gene regulators (CCND1, HIF1A); and others, including some novel gene candidates (CREB1, FGF20, IFI27), that have never been implicated in EC earlier. The expression of hsa-miR-433-3p showed significant predictive relevance (Fold Change = 1.8, AUC = 0.736, Mann-Whitney test p-value = 6.1 e- 14) suggesting its predictive relevance in assessing patients' response to chemotherapy. The hsamiR- 188-3p targets autophagic and apoptotic regulators and its upregulation in endometriosis may be used as for the early stage diagnostic purpose. The hsa-miR-502-5p targets SET D8, T RAF2 and others and suggests additional genomic/epigenomic molecular targets for promising therapeutic interventions in EC. Predicted miRNAs target a number of mRNAs having varied functional impacts and offer an in-depth mechanistic insights for expatiating the biological and regulatory role in EC.Communicated by Ramaswamy H. Sarma.
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Abstract

In recent years, exploring the potential of miRNAs as novel diagnostic, prognostic and diagnostic markers have gained much attention. In current study, we conducted an in-depth circRNA-miRNA-mRNA interactome to reveal significant molecular processes and biological pathways putatively associated with endometrial cancer (EC). Firstly, we retrieved two circRNAs from circad, hsa_circ_0002577 & hsa_circ_0109046, based on their association with the EC. Subsequently, we predicted miRNAs sponging sites in the two circRNAs and the potential target mRNAs of the predicted miRNAs. Sequestered miRNAs target a number of oncogenes (CBL, MET, KRAS), tumor suppressor (CFT R), receptor protein kinases & GT Pase (MET, KRAS, RAB1B), methyltransferases (SET D8), receptors associated factors (T RAF2, GRB2), growth factors (FGF20), autophagy (BECN1, AT G14), apoptotic regulators (BCL2), transcription factors (T Fs) (CREB1, RUNX1, RUNX2) and gene regulators (CCND1, HIF1A); and others, including some novel gene candidates (CREB1, FGF20, IFI27), that have never been implicated in EC earlier. The expression of hsa-miR-433-3p showed significant predictive relevance (Fold Change = 1.8, AUC = 0.736, Mann-Whitney test p-value = 6.1 e- 14) suggesting its predictive relevance in assessing patients’ response to chemotherapy. The hsamiR- 188-3p targets autophagic and apoptotic regulators and its upregulation in endometriosis may be used as for the early stage diagnostic purpose. The hsa-miR-502-5p targets SET D8, T RAF2 and others and suggests additional genomic/epigenomic molecular targets for promising therapeutic interventions in EC. Predicted miRNAs target a number of mRNAs having varied functional impacts and offer an in-depth mechanistic insights for expatiating the biological and regulatory role in EC.

Acknowledgement

The TCD acknowledges Mohanlal Sukhadia University for the Infrastructure Facility. Disclosure statement No potential conflict of interest was reported by the author(s).

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endometriosis

MeSH descriptors

Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms MicroRNAs MicroRNAs MicroRNAs MicroRNAs MicroRNAs MicroRNAs MicroRNAs MicroRNAs MicroRNAs

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