Abstract
Background
Deciphering new molecules related to the breast cancer subtypes is crucial for prognosis and determining a better strategy for targeted therapy. In this study, we aimed to model ceRNAs networks in luminal A and luminal B subtypes of breast cancer and then delve deeper into the role of two candidate lncRNAs in breast tumors.
Methods
We constructed two networks as a regulatory model based on our previously identified transcription factors (TFs) and miRNAs with associated lncRNAs. Then, we highlighted the role of some lncRNAs in luminal subtypes of breast cancer using available online databases. Furthermore, we empirically quantified the expression levels of two candidate lncRNAs (DRAIC and TP53TG1) in breast tumors and normal tissues.
Results
Here, we proposed a regulatory model for TFs–miRNAs–lncRNAs in luminal subtypes of breast cancer. We found 18 and 17 differentially expressed lncRNAs in luminal A and luminal B subtypes, respectively. Of these lncRNAs, 16 were associated with breast cancer patients' RFS and/or OS rates. Well-known lncRNAs like HOTAIR and MALAT1 were identified as central factors associated with patients’ survival rates in both networks. Based on the results acquired from our comprehensive in-silico data analysis, we carried out clinical experiments on two less-known lncRNAs, DRAIC and TP53TG1, and found a significant association between them with luminal subtypes of breast cancer. Interestingly, we discovered a significant association between DRAIC and TP53TG1 lncRNAs with ER- and PR-positive samples and lymph-node invasion in breast cancer patients.
Conclusion
According to the results, DRAIC and TP53TG1 lncRNAs are overexpressed in breast tumors and may play an oncogenic role with a moderate value of prognosis for luminal subtypes of breast cancer.
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Data availability
The data that support the findings of this study are available.
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This research was conducted using the authors’ personal money.
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JM: conceptualization, investigation, formal analysis, writing original draft, figures illustration, and writing—review and editing. EE: investigation, formal analysis, and writing—original draft.
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This study was approved by the ethics committee of Iran National Tumor Bank (INTB). All procedures performed in the study involving human participants were in accordance with the ethical standards and with the Helsinki Declaration and its later amendments.
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Motalebzadeh, J., Eskandari, E. Comprehensive analysis of DRAIC and TP53TG1 in breast cancer luminal subtypes through the construction of lncRNAs regulatory model. Breast Cancer 29, 1050–1066 (2022). https://doi.org/10.1007/s12282-022-01385-7
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DOI: https://doi.org/10.1007/s12282-022-01385-7