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INNOSC Theranostics and
Pharmacological Sciences Enhancers and SEs in cancer treatment
toxicity, enhanced permeability, and precise targeting of understand the complex molecular mechanisms of eRNAs
cancer cells, offer a significant benefit in the treatment of in tumorigenesis. Moreover, a better understanding of
cancer and aid in addressing the constraints and obstacles enhancers and SEs structure, as well as reliable structural
associated with traditional cancer treatment modalities conformations of eRNAs and their interactions with target
115
Huang et al. made a significant discovery using ChIP- genes in three-dimensional space, is needed. Finally,
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seq to identify top SE-associated genes, which they CRISPR genome/epigenome-editing and enhancer-
found to be promising oncogenes in pancreatic ductal targeting drugs, such as BET inhibitors, present promising
adenocarcinoma (PDAC). These genes were shown to be tools for correcting enhancers and SEs abnormalities in
highly susceptible to treatment with the cyclin-dependent cancer therapy.
kinase 7 inhibitor, THZ1, and BRD4 inhibitor, JQ1. In
addition, it was shown that utilizing NPs containing a Acknowledgments
significant amount of JQ1, in combination with THZ1, None.
could serve as a potentially effective therapeutic approach
for treating PDAC by inhibiting SE-associated oncogenic Funding
transcription. While the study presents a novel approach
for targeting SEs through the application of nanocarriers None.
and opens new horizons for cancer treatment, the risks Conflict of interest
and hazards related to NPs still need to be addressed before
approval for clinical applications. The authors declare that they have no competing interests.
6. Conclusion and perspectives Author contributions
Enhancers play a crucial role in transcription regulation. Conceptualization: All authors
The aberrant activation of enhancers and SEs due to Writing – original draft: Pouya Sarvari, Pourya Sarvari,
chromosomal rearrangements and genetic/epigenetic Ivonne Ramirez-Diaz
variation drives oncogene activation, resulting in Writing – review & editing: Karla Rubio
uncontrolled cell proliferation, resistance to apoptosis,
and, consequently, tumor formation and progression. Ethics approval and consent to participate
Enhancer-mediated regulation of genes is determined not Not applicable.
only by their location but especially by their capability to
physically bind to an appropriate promoter, which can even Consent for publication
occur in a different chromosome topology. The epigenetic Not applicable.
state of enhancers is crucial for their function, often used
to identify their genomic locations. Active enhancers Availability of data
initiate the production of eRNAs and usually possess high
levels of H3K4me1 and H3K27ac. However, more factors Not applicable.
are required for robust enhancer identification. References
The recent discovery of eRNAs adds another layer of
complexity to the human transcriptome, encouraging 1. Maston GA, Evans SK, Green MR. Transcriptional regulatory
elements in the human genome. Annu Rev Genomics Hum
intense research on the features and potential functions Genet. 2006;7(1):29-59.
of this new class of ncRNAs. Evidence suggests that
eRNAs may be powerful biological markers in cancer doi: 10.1146/annurev.genom.7.080505.115623
treatment and therapy. Abundant evidence shows that 2. Kvon EZ, Waymack R, Gad M, Wunderlich Z. Enhancer
eRNAs are abnormally expressed in various cancers and redundancy in development and disease. Nat Rev Genet.
that their expression is closely related to tumorigenesis. 2021;22(5):324-336.
Investigations into these eRNAs reveal new oncogenic doi: 10.1038/s41576-020-00311-x
pathway activation in tumor cells and propose new 3. Vieira KF, Levings PP, Hill MA, et al. Recruitment of
potential targets for combination therapies. However, transcription complexes to the beta-globin gene locus
these findings on eRNAs and their association with cancer in vivo and in vitro. J Biol Chem. 2004;279(48):50350-50357.
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leaving the underlying molecular mechanisms involved 4. Rodriguez-Jato S, Nicholls RD, Driscoll DJ, Yang TP.
unclear. Further molecular analyses are required to fully Characterization of cis-and trans-acting elements in the
Volume 7 Issue 3 (2024) 8 doi: 10.36922/itps.3654

