Novel protein drives cancer progression

Date:
July 6, 2020
Source:
National University of Singapore
Summary:
Researchers have discovered a protein that drives the progression
of esophageal cancer and liver cancer and it could be a promising
target for cancer drug development.



FULL STORY ========================================================================== Cancers arise when the genetic code of normal cells is altered, causing excessive growth. Researchers from the Cancer Science Institute of
Singapore (CSI Singapore) at the National University of Singapore (NUS)
have discovered a protein that drives the growth of cancers of the
esophagus or liver by altering the genetic code in a novel way.


==========================================================================
The protein, death associated protein 3 (DAP3), represses a process called adenosine-to-inosine (A-to-I) RNA editing that normally corrects the
genetic code to ensure that genes are expressed correctly. By inhibiting
RNA editing, DAP3 acts as an oncogene -- a gene that has the potential
to cause cancer. This discovery offers the potential of developing novel
drugs that target DAP3 for cancer treatment.

The study was led by Assistant Professor Polly Chen, a Principal
Investigator at CSI Singapore, and the findings were published in the scientific journal Science Advances on 17 June 2020.

Understanding A-to-I RNA editing RNAs are one of the most important
classes of molecules in cells. They not only convert the genetic
information stored in DNA to proteins, but also play critical regulatory
roles in various biological processes. RNA editing is a process in
which RNA is changed after it is made from DNA, resulting in an altered
gene product. In humans, the most common type of RNA editing is A-to-
I editing, which is mediated by ADAR proteins (ADAR1 and ADAR2). In
the past decade, many studies have reported that the accumulation of deleterious changes in A-to-I RNA editing can trigger a cell to develop
into cancer. However, the current knowledge of how the A-to-I RNA editing process is regulated in cancer is still limited.

The CSI Singapore research team therefore conducted a research study
to understand how DAP3 -- the interacting protein of the A-to-I RNA
editing catalytic enzymes (ADAR1 and ADAR2) -- regulates this process
in cancer cells.

Promising drug target for cancer treatment The team demonstrated that
DAP3 could destroy the binding of ADAR2 protein to its target RNAs,
thereby inhibiting the A-to-I RNA editing in cancer cells.

This suppression is likely to be one of the pathways by which DAP3 could promote cancer development.

Their analysis also revealed that the expression of DAP3 is elevated in
17 types of cancer. Further experiments demonstrated that DAP3 acted as
an oncogene in esophageal cancer and liver cancer cells. Interestingly,
they also identified the gene PDZD7, one of DAP3-inhibited editing
targets and discovered that altered editing of PDZD7 generated a new
PDZD7 protein product which contributed to the DAP3-driven tumor growth.

Overall, these observations shed light on the complexity of the regulation
of the A-to-I RNA editing process in cancer cells, and suggest that DAP3
could be a promising target for future cancer drug development.

"With this new knowledge, we can now look into how we can intervene in
the interactions between DAP3 and ADAR proteins in order to interfere
with cancer- promoting processes mediated by RNA editing in the cell,"
said research leader Asst Prof Chen.


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


========================================================================== Journal Reference:
1. Jian Han, Omer An, HuiQi Hong, Tim Hon Man Chan, Yangyang Song,
Haoqing
Shen, Sze Jing Tang, Jaymie Siqi Lin, Vanessa Hui En Ng, Daryl Jin
Tai Tay, Fernando Bellido Molias, Priyankaa Pitcheshwar, Hui Qing
Tan, Henry Yang, Leilei Chen. Suppression of adenosine-to-inosine
(A-to-I) RNA editome by death associated protein 3 (DAP3) promotes
cancer progression.

Science Advances, 2020; 6 (25): eaba5136 DOI: 10.1126/sciadv.aba5136 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200706114001.htm

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