Super-enhancers: The villain fueling certain cancers
Researchers identify a regulatory RNA molecule that can help block
expression of a powerful cancer-promoting gene

Date:
October 5, 2021
Source:
Tokyo Medical and Dental University
Summary:
Researchers identified a small RNA molecule called miR-766-5p that
reduces expression of MYC, a critical cancer-promoting gene. This
microRNA reduces levels of proteins CBP and BRD4, which are both
involved in super-enhancer (SE) formation. SEs form in areas of
DNA that can fuel MYC expression and tumor progression. This
study provides strong evidence for developing miR-766-5p as a
novel therapeutic to treat MYC-driven cancers.



FULL STORY ==========================================================================
In a recent study published in Cancer Research, a team led by researchers
at Tokyo Medical and Dental University (TMDU) identified a specific small
RNA molecule, called a microRNA (miRNA or miR), that has the potential
to be used as an anti-cancer therapeutic. The new research indicates
that the molecule, called miR-766-5p, can significantly reduce levels
of the oncogene MYC -- a specific gene that is expressed at high levels
in tumor cells and helps fuel cancer growth and progression.


==========================================================================
At its most basic level, cancer is driven by abnormal and uncontrolled
gene expression. Numerous different molecular mechanisms contribute
to the activation and overexpression of oncogenes in cancer. MiRNAs
work as negative regulators of gene expression. This means that they
can directly bind and interact with certain gene messages and block
them from being translated into a protein. Therefore, any molecular
pathway controlled by that specific protein is also affected by this miRNA-mediated regulation. In a previous study, the TMDU group used
cell culture experiments to demonstrate that treating cancer cells with miR-766-5p resulted in lower MYC expression and inhibited cancer cell
growth rates. Following these intriguing findings, the group aimed to
determine the specific mechanism behind these results.

"MYC is a critical oncogene in many tumor types," says lead author
of the study Yasuyuki Gen. "It can promote cancer cell proliferation,
can suppress the body's immune response to fighting the cancer, and can generally be the main driver of tumor progression in many patients."
The researchers found that miR-766-5p could directly target and reduce expression of two proteins called CBP and BRD4. CBP can induce a molecular change called acetylation that causes DNA to become more "open," which
allows genes present in that area to be more easily expressed. BRD4 can
then be recruited to these sites and help promote transcription of these
gene messages.

"Areas of DNA with high activity of proteins like CBP and BRD4 are
known as super-enhancers," explains Johji Inazawa, senior author. "Many
cancer cells develop super-enhancers near oncogenes, like MYC, that drive increased oncogene expression and therefore promote cancer." The team
then experimentally treated cells with a synthetic version of miR-766- 5p, finding that the resulting suppression of CBP and BRD4 caused decreased
MYC levels in cancer cells, but not in normal cells. Additionally,
tumors that were engrafted in lab mice showed significantly suppressed
growth when treated with miR-766-5p compared with a control miRNA.

"Our findings suggest that miR-766-5p-mediated control of CBP and
BRD4 blocks formation of the super-enhancers that contribute to MYC overexpression in cancer cells," explains Gen.

In recent years, efforts have been made to develop specific miRNAs into targeted therapies for various cancers. This study provides considerable evidence that miR-766-5p could be used to fight MYC-driven cancers by
targeting super-enhancers.

========================================================================== Story Source: Materials provided by
Tokyo_Medical_and_Dental_University. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Yasuyuki Gen, Tomoki Muramatsu, Jun Inoue, Johji Inazawa. miR-766-5p
targets super-enhancers by downregulating CBP and BRD4. Cancer
Research, 2021; canres.0649.2021 DOI: 10.1158/0008-5472.CAN-21-0649 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211005124701.htm

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