New findings may contribute to better diagnosis and treatment of liver
cancer

Date:
January 12, 2022
Source:
Karolinska Institutet
Summary:
In a new study, researchers have identified the presence of a
specific connection between a protein and an lncRNA molecule in
liver cancer. By increasing the presence of the lncRNA molecule,
the fat depots of the tumor cell decrease, which causes the
division of tumor cells to cease, and they eventually die. The
study contributes to increased knowledge that can add to a better
diagnosis and future cancer treatments.



FULL STORY ==========================================================================
In a new study, researchers at Karolinska Institutet have identified
the presence of a specific connection between a protein and an lncRNA
molecule in liver cancer. By increasing the presence of the lncRNA
molecule, the fat depots of the tumor cell decrease, which causes the
division of tumor cells to cease, and they eventually die. The study,
published in the journal Gut, contributes to increased knowledge that
can add to a better diagnosis and future cancer treatments.


==========================================================================
Our genome gives our cells instructions that determine each cell type's
highly specialized function. The information is sent out using two
different types of RNA molecules: coding RNA that converts DNA into
proteins and non-coding RNA that do not produce proteins.

Because non-coding RNA molecules do not produce proteins, they have not
been the main focus of research in the past, even though they amount
to approximately 97 per cent of the RNA in our body. However, certain
proteins, called RNA-binding proteins, have been shown to play a crucial
role in cancer because of their ability to affect several different
properties of RNA molecules.

"With the help of tissue material donated by patients with liver cancer,
we have been able to map both the coding and non-coding part of our genome
to identify which RNA-binding proteins have a high presence in liver
cancer cells," says the study's senior author Claudia Kutter, researcher
at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. "We found that many of these proteins interacted with a long
type of non-coding RNA molecules, so-called lncRNA." The research team conducted a more detailed study of a specific pairing of a RNA-binding
protein (CCT3) and an lncRNA molecule (LINC00326). Using advanced CRISPR technology, they were able to both reduce and increase the amount of the protein and the lncRNA to see how it affected the cancer cells. When
the lncRNA was increased, the fat depots of the tumor cell decreased,
the cell division ceased and many of the cancer cells died. Following
the laboratory studies, the results were also verified in vivo.

Many more combinations to investigate The researchers' discovery provides
an insight into the interaction between RNA-binding proteins and lncRNA molecules, and contributes to a better scientific understanding of their
role in tumors.

"The activities of the CCT3-LINC00326 pair can already be used in liver
cancer diagnosis and prognosis," says the study's first author Jonas
No/rskov So/ ndergaard, researcher in Kutter's research group. "However,
the knowledge of this particular pairing is just the beginning and there
are many more combinations of RNA-binding proteins and lncRNA molecules
that we will further investigate. In the long run, these findings can
help to contribute to new and effective treatments such as RNA-based
treatments that target only the diseased cells, with the possibility of reducing side effects." The study was supported by grants from the Knut
and Alice Wallenberg Foundation, the Ruth and Richard Julin foundation, a SFO-SciLifeLab fellowship, the Swedish Research Council, the Lillian Sagen
and Curt Ericsson Research Foundation, Go"sta Miltons Foundation, the
Chinese Scholarship Council, KI-KID funding, SNIC projects, Nilsson-Ehle Endowments, Barts and London Charity, Cancer Research UK, AIRC Fellowship
for Abroad, Tornspiran Foundation and the Swedish Society of Medicine.

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


========================================================================== Journal Reference:
1. Jonas No/rskov So/ndergaard, Christian Sommerauer, Ionut Atanasoai,
Laura
C Hinte, Keyi Geng, Giulia Guiducci, Lars Bra"utigam, Myriam Aouadi,
Lovorka Stojic, Isabel Barragan, Claudia Kutter. CCT3-LINC00326
axis regulates hepatocarcinogenic lipid metabolism. Gut, 2022;
gutjnl-2021- 325109 DOI: 10.1136/gutjnl-2021-325109 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220112093958.htm
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