Skip to main content
Log in

Genomic analysis of nuclear receptors and miRNAs identifies a role for the NR3C1/miR-200 axis in colon cancer

  • Research Article
  • Published:
Genes & Genomics Aims and scope Submit manuscript

A Publisher Correction to this article was published on 14 July 2021

This article has been updated

Abstract

Background

Nuclear receptors (NRs) are crucial transcription factors involved in cell proliferation, metabolism and homeostasis. Through the development of novel genomic approaches, unknown NR functions have recently been uncovered. NR networks derived from gene expression profiles revealed that NRs are tightly linked to human disease and that targeting these links could provide new therapeutic options. MicroRNAs (miRNAs) have known functions as transcriptional regulators of NR function.

Objective

I attempted to construct an NR-miRNA transcriptional network based on genomic data from human cancer.

Methods

I performed comprehensive analysis with genomic data. Correlation, clustering and survival analysis were done to identify the NR and miRNA correlation in cancer.

Results

Correlation analysis of genomic data revealed relationships between the expression levels of several NRs and miRNAs in human cancer. Based on my NR-miRNA correlation data, I found that NR3C1 expression was highly correlated with that of miR-200 in colon cancer. In most cases, miRNAs suppress expression of their target genes. Thus, miRNAs function as negative regulators during transcription. My analysis revealed that the miR-200 expression level is negatively correlated with that of NR3C1, demonstrating that miR-200 is a negative regulator of NR3C1 in colon cancer. It is known that miR-200 is a master regulator of EMT and that NR3C1 has a link with an EMT marker.

Conclusions

Overall, my genomic analysis revealed that the NR3C1 expression level is correlated with that of miR-200 and that this functional relationship might contribute to colon cancer cell survival. Modulating this axis could be a promising target for treating colon cancer patients.

Graphic abstract

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

Similar content being viewed by others

Change history

References

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  Google Scholar 

  • Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ (2006) Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 126:789–799

    Article  CAS  Google Scholar 

  • Carroll JS, Liu XS, Brodsky AS, Li W, Meyer CA, Szary AJ, Eeckhoute J, Shao W, Hestermann EV, Geistlinger TR et al (2005) Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell 122:33–43

    Article  CAS  Google Scholar 

  • Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95:14863–14868

    Article  CAS  Google Scholar 

  • Jordan VC (2001) Selective estrogen receptor modulation: a personal perspective. Cancer Res 61:5683–5687

    CAS  PubMed  Google Scholar 

  • Lin S, Gregory RI (2015) MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 15:321–333

    Article  CAS  Google Scholar 

  • Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P et al (1995) The nuclear receptor superfamily: the second decade. Cell 83:835–839

    Article  CAS  Google Scholar 

  • McKenna NJ, Cooney AJ, DeMayo FJ, Downes M, Glass CK, Lanz RB, Lazar MA, Mangelsdorf DJ, Moore DD, Qin J et al (2009) Minireview: evolution of NURSA, the nuclear receptor signaling atlas. Mol Endocrinol 23:740–746

    Article  CAS  Google Scholar 

  • McKenna NJ, Evans RM, O’Malley BW (2014) Nuclear receptor signaling: a home for nuclear receptor and coregulator signaling research. Nucl Recept Signal 12:e006

    Article  Google Scholar 

  • Park SM, Gaur AB, Lengyel E, Peter ME (2008) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 22:894–907

    Article  CAS  Google Scholar 

  • Park YY, Choi HS, Lee JS (2010) Systems-level analysis of gene expression data revealed NR0B2/SHP as potential tumor suppressor in human liver cancer. Mol Cells 30:485–491

    Article  CAS  Google Scholar 

  • Park YY, Kim K, Kim SB, Hennessy BT, Kim SM, Park ES, Lim JY, Li J, Lu Y, Gonzalez-Angulo AM et al (2012) Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. EMBO Mol Med 4:52–67

    Article  CAS  Google Scholar 

  • Roscigno M, Sangalli M, Mazzoccoli B, Scattoni V, Da Pozzo L, Rigatti P (2005) Medical therapy of prostate cancer. A review. Minerva Urol Nefrol 57:71–84

    CAS  PubMed  Google Scholar 

  • Sladek FM (2003) Nuclear receptors as drug targets: new developments in coregulators, orphan receptors and major therapeutic areas. Expert Opin Ther Targets 7:679–684

    Article  CAS  Google Scholar 

  • Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S, Demichelis F, Helgeson BE, Laxman B, Morris DS et al (2008) The role of SPINK1 in ETS rearrangement-negative prostate cancers. Cancer Cell 13:519–528

    Article  CAS  Google Scholar 

  • Yang X, Downes M, Yu RT, Bookout AL, He W, Straume M, Mangelsdorf DJ, Evans RM (2006) Nuclear receptor expression links the circadian clock to metabolism. Cell 126:801–810

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Chung-Ang University Research Grants in 2020 and by the National Research Foundation (NRF-2020R1A2C1003216).

Author information

Authors and Affiliations

Authors

Contributions

YYP generated the hypothesis, analyzed the data, and wrote the manuscript. YYP interpreted the data and edited the manuscript.

Corresponding author

Correspondence to Yun-Yong Park.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interests.

Additional information

Publisher’s Note

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

The original online version of this article was revised as the "Graphical abstract B" was asked to be removed but it has not been removed during proof corrections as informed by the author. The article has now been corrected

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, YY. Genomic analysis of nuclear receptors and miRNAs identifies a role for the NR3C1/miR-200 axis in colon cancer. Genes Genom 43, 913–920 (2021). https://doi.org/10.1007/s13258-021-01112-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13258-021-01112-0

Keywords

Navigation