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Identification of non-coding RNA related prognosis biomarkers based on ceRNA network in thyroid cancer
Xin Fang1,2, Xiliang Chen2, Jingquan Gao3
1Department of General Surgery II, Daqing Oilfield General Hospital, Daqing, China.
Abstract:
Introduction: Thyroid cancer (THCA) has become a serious malignant tumor worldwide. Identification of non-coding RNA related regulators is very necessary to improve the knowledge of THCA treatment. The aim of this study was to identify novel therapeutic targets and prognosis biomarkers for predicting pathological characteristics and subsequently treating THCA. Methods: We investigated the alterations of miRNAs, mRNAs and lncRNAs in THCA. Functional enrichment and clustering analysis were conducted for these aberrantly expressed RNAs. Multiple interaction networks among miRNAs, mRNAs and lncRNAs were constructed and the functional modules associated with THCA patients' prognosis were identified. Furthermore, we evaluated the prognostic roles of the important miRNAs, mRNAs and lncRNAs in THCA and investigated the regulatory potential of non-coding RNAs on immune cell infiltration. Results: We firstly identified that miR-4709-3p and miR-146b-3p could significantly classify patients into high/low risk groups, which may be potential prognosis biomarkers of THCA. Secondly, we constructed a THCA-related miRNA-mRNA network, which displayed small world network topological characters. Two THCA-related functional modules were identified from the miRNA-mRNA network by MCODE. Results showed that two modules could implicate in known cancer pathways, such as apoptosis and focal adhesion. Thirdly, a THCA-related miRNA-lncRNA network was constructed. A subnetwork of miRNA-lncRNA network showed strong prognosis effect in THCA. Fourthly, we constructed a THCA-related mRNA-lncRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as AC068138, BCL2, miR-21 and miR-146b, which had good prognosis effect in THCA. Immune infiltration results showed that lncRNAs LA16c-329F2, RP11-395N3, RP11-423H2, RP11-399B17 and RP11-1036E20 were high related to neutrophil and dendritic cell infiltration. Discussion: Non-coding RNA-mediated gene regulatory network has the strong regulatory potential in pathological processes of THCA. All these results could help us uncover the non-coding RNA-mediated regulatory mechanism in THCA.
Insights
This study identifies key non-coding RNAs, like miR-4709-3p and miR-146b-3p, as potential biomarkers for thyroid cancer (THCA) prognosis. It also reveals complex regulatory networks influencing THCA progression and immune cell infiltration.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Thyroid cancer (THCA) is a significant global health concern.
- Understanding non-coding RNA (ncRNA) regulators is crucial for advancing THCA treatment strategies.
Purpose of the Study:
- To identify novel therapeutic targets and prognostic biomarkers for THCA.
- To elucidate the roles of microRNAs (miRNAs), messenger RNAs (mRNAs), and long non-coding RNAs (lncRNAs) in THCA pathology.
- To investigate ncRNA-mediated regulatory networks and their impact on immune cell infiltration in THCA.
Main Methods:
- Analysis of aberrantly expressed miRNAs, mRNAs, and lncRNAs in THCA.
- Functional enrichment and clustering analysis of differentially expressed RNAs.
- Construction and analysis of multi-layered interaction networks (miRNA-mRNA, miRNA-lncRNA, mRNA-lncRNA).
- Evaluation of prognostic significance and immune cell infiltration correlations.
Main Results:
- Identified miR-4709-3p and miR-146b-3p as potential prognostic biomarkers for classifying THCA patients.
- Constructed a miRNA-mRNA network with significant modules implicated in apoptosis and focal adhesion pathways.
- Revealed prognostic value in miRNA-lncRNA subnetworks and identified key lncRNA-miRNA-mRNA crosstalk (e.g., AC068138, BCL2, miR-21, miR-146b).
- Found specific lncRNAs (LA16c-329F2, RP11-395N3, etc.) strongly correlated with neutrophil and dendritic cell infiltration.
Conclusions:
- ncRNA-mediated gene regulatory networks play a significant role in THCA pathological processes.
- The identified biomarkers and networks offer potential for improved THCA diagnosis, prognosis, and therapeutic strategies.
- Understanding these regulatory mechanisms can enhance knowledge of THCA pathogenesis and immune responses.
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