Skip to main content

Advertisement

Log in

Comprehensive analysis of DRAIC and TP53TG1 in breast cancer luminal subtypes through the construction of lncRNAs regulatory model

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data availability

The data that support the findings of this study are available.

References

  1. Pal B, et al. A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast. EMBO J. 2021;40(11): e107333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol. 2014;5(3):412.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Reis-Filho JS, et al. Molecular profiling: moving away from tumor philately. Sci Transl Med. 2010;2(47):43–7.

    Article  Google Scholar 

  4. Creighton CJ. The molecular profile of luminal B breast cancer. Biologics. 2012;6:289.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Li A, et al. H19, a long non-coding RNA, mediates transcription factors and target genes through interference of microRNAs in pan-cancer. Mol Ther-Nucleic Acids. 2020;21:180–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wang J, et al. Construction and comprehensive analysis of dysregulated long non-coding RNA-associated competing endogenous RNA network in clear cell renal cell carcinoma. J Cell Biochem. 2019;120(2):2576–93.

    Article  CAS  Google Scholar 

  7. Bai H, et al. Comprehensive analysis of lncRNA–miRNA–mRNA during proliferative phase of rat liver regeneration. J Cell Physiol. 2019;234(10):18897–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Eskandari E, Motalebzadeh J. Transcriptomics-based screening of molecular signatures associated with patients overall survival and their key regulators in subtypes of breast cancer. Cancer Genet. 2019;239:62–74.

    Article  CAS  PubMed  Google Scholar 

  9. Zhao H, et al. LncTarD: a manually-curated database of experimentally-supported functional lncRNA–target regulations in human diseases. Nucleic Acids Res. 2020;48(D1):D118–26.

    CAS  PubMed  Google Scholar 

  10. Cheng L, et al. LncRNA2Target v2. 0: a comprehensive database for target genes of lncRNAs in human and mouse. Nucleic Acids Res. 2019;47:D140–4.

    Article  CAS  PubMed  Google Scholar 

  11. Kang J, et al. RNAInter v4. 0: RNA interactome repository with redefined confidence scoring system and improved accessibility. Nucleic Acids Res. 2021;50:D326-332.

    Article  PubMed Central  Google Scholar 

  12. Gong J, et al. RISE: a database of RNA interactome from sequencing experiments. Nucleic Acids Res. 2018;46(D1):D194–201.

    Article  CAS  PubMed  Google Scholar 

  13. Tang Z, et al. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47(W1):W556–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chandrashekar DS, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19(8):649–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lánczky A, et al. miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 2016;160(3):439–46.

    Article  PubMed  Google Scholar 

  16. Perron U, Provero P, Molineris I. In silico prediction of lncRNA function using tissue specific and evolutionary conserved expression. BMC Bioinform. 2017;18(5):29–39.

    Google Scholar 

  17. Kun C, Lei Y. Microscopic traffic-emission simulation and case study for evaluation of traffic control strategies. J Transp Syst Eng Inf Technol. 2007;7(1):93–9.

    Google Scholar 

  18. Motalebzadeh J, Eskandari E. Transcription factors linked to the molecular signatures in the development of hepatocellular carcinoma on a cirrhotic background. Med Oncol. 2021;38(10):1–12.

    Article  Google Scholar 

  19. Sivadas A, Kok VC, Ng K-L. Multi-omics analyses provide novel biological insights to distinguish lobular ductal types of invasive breast cancers. Breast Cancer Res Treat. 2022;193(2):361–79.

    Article  CAS  PubMed  Google Scholar 

  20. Sørensen KP, et al. Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer. Breast Cancer Res Treat. 2013;142(3):529–36.

    Article  PubMed  Google Scholar 

  21. Li Z-X, et al. MALAT1: a potential biomarker in cancer. Cancer Manag Res. 2018;10:6757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chen Q, Zhu C, Jin Y. The oncogenic and tumor suppressive functions of the long noncoding RNA MALAT1: an emerging controversy. Front Genet. 2020;11:93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Elias-Rizk T, et al. The long non coding RNA H19 as a biomarker for breast cancer diagnosis in Lebanese women. Sci Rep. 2020;10(1):1–7.

    Article  Google Scholar 

  24. Li W, et al. The FOXN3-NEAT1-SIN3A repressor complex promotes progression of hormonally responsive breast cancer. J Clin Investig. 2017;127(9):3421–40.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Guo F, et al. miR-589-3p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R. Int J Mol Med. 2020;46(3):989–1002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang J, Guo S, Jia B. Down-regulation of long non-coding RNA MEG3 serves as an unfavorable risk factor for survival of patients with breast cancer. Eur Rev Med Pharmacol Sci. 2016;20(24):5143–7.

    PubMed  Google Scholar 

  27. Cheng K, et al. lncRNA GAS5 inhibits colorectal cancer cell proliferation via the miR-182-5p/FOXO3a axis. Oncol Rep. 2018;40(4):2371–80.

    CAS  PubMed  Google Scholar 

  28. Sakurai K, et al. The lncRNA DRAIC/PCAT29 locus constitutes a tumor-suppressive nexus. Mol Cancer Res. 2015;13(5):828–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sun M, et al. Discovery, annotation, and functional analysis of long noncoding RNAs controlling cell-cycle gene expression and proliferation in breast cancer cells. Mol Cell. 2015;59(4):698–711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhao D, Dong J-T. Upregulation of long non-coding RNA DRAIC correlates with adverse features of breast cancer. Non-coding RNA. 2018;4(4):39.

    Article  CAS  PubMed Central  Google Scholar 

  31. Kok VC, et al. Cross-platform in-silico analyses exploring tumor immune microenvironment with prognostic value in triple-negative breast cancer. Breast Cancer (Dove Medical Press). 2022;14:85–99.

    CAS  Google Scholar 

  32. Saha S, et al. Long noncoding RNA DRAIC inhibits prostate cancer progression by interacting with IKK to inhibit NF-κB activation. Can Res. 2020;80(5):950–63.

    Article  CAS  Google Scholar 

  33. Zhang Z, et al. LncRNA DRAIC inhibits proliferation and metastasis of gastric cancer cells through interfering with NFRKB deubiquitination mediated by UCHL5. Cell Mol Biol Lett. 2020;25(1):1–17.

    Article  Google Scholar 

  34. Diaz-Lagares A, et al. Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer. Proc Natl Acad Sci. 2016;113(47):E7535–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shao M, et al. Survival analysis for long noncoding RNAs identifies TP53TG1 as an antioncogenic target for the breast cancer. J Cell Physiol. 2020;235(10):6574–81.

    Article  CAS  PubMed  Google Scholar 

  36. Xiao H, et al. TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis. Cell Biosci. 2018;8(1):1–13.

    Article  Google Scholar 

  37. Xue X, et al. LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogene. 2016;35(21):2746–55.

    Article  CAS  PubMed  Google Scholar 

  38. Lu Q, et al. LncRNA TP53TG1 promotes the growth and migration of hepatocellular carcinoma cells via activation of ERK signaling. Non-coding RNA. 2021;7(3):52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang H, et al. Long non-coding RNA TP53TG1 upregulates shcbp1 to promote retinoblastoma progression by sponging miR-33b. Cell Transplant. 2021;30:09636897211025223.

    Article  PubMed Central  Google Scholar 

  40. Zhang Y, et al. Long noncoding RNA TP53TG1 promotes pancreatic ductal adenocarcinoma development by acting as a molecular sponge of microRNA-96. Cancer Sci. 2019;110(9):2760–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was conducted using the authors’ personal money.

Author information

Authors and Affiliations

Authors

Contributions

JM: conceptualization, investigation, formal analysis, writing original draft, figures illustration, and writing—review and editing. EE: investigation, formal analysis, and writing—original draft.

Corresponding author

Correspondence to Jamshid Motalebzadeh.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical standards

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.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-022-01385-7

Keywords

Navigation