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
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Change history
14 July 2021
A Correction to this paper has been published: https://doi.org/10.1007/s13258-021-01132-w
References
Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233
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
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
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
Jordan VC (2001) Selective estrogen receptor modulation: a personal perspective. Cancer Res 61:5683–5687
Lin S, Gregory RI (2015) MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 15:321–333
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
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
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
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
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
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
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
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
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
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
Acknowledgements
This research was supported by the Chung-Ang University Research Grants in 2020 and by the National Research Foundation (NRF-2020R1A2C1003216).
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YYP generated the hypothesis, analyzed the data, and wrote the manuscript. YYP interpreted the data and edited the manuscript.
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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
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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
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DOI: https://doi.org/10.1007/s13258-021-01112-0