Cancer Sci: Scientists identify key molecular targets against pancreatic cancer in humans

Today, pancreatic cancer is still one of the deadliest malignancies faced by the global population, because the 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) patients is only about 3%, so PDAC is difficult to treat surgically worldwide, in order to develop new therapeutic strategies, researchers need to better understand the biology
of PDAC at the molecular level 。 Recently, a research report entitled "Identification of a novel target of SETD1A histone methyltransferase and the clinical significance in pancreatic cancer" published in the international journal Cancer Science, Scientists from Tokyo University of Medicine and Dentistry and other institutions have identified a new type of targeted gene that may have strong clinical significance
for PDAC cases.

Previous results have shown that cancer cells can express a high-level special enzyme encoded by the SETD1A gene, histone H3K4 methyltransferase, which can be added to the histone (necessary building blocks of chromatin) of specific targeted genes through methylation chemical groups, a process called methylation process, however, the molecular mechanism that induces overexpression of this enzyme and its effect on cancer cells.
Researchers don't know
.

When histones are methylated, targeted genes are activated, which is particularly interesting if the targeted gene for SETD1A supports cancer development and progression, so the researchers are very interested in understanding the key role
that SETD1A overexpression plays in PDAC 。 Researcher Takeshi Ishii said that although previous results have shown that SETD1A is overexpressed and loaded in a variety of cancers, such as stomach cancer and lung cancer, we do not know its specific molecular events in PDAC, and the targeted gene for SETD1A in PDAC has not yet been identified or identified
.

Scientists identify key molecular targets against pancreatic cancer in humans
.

Image source: Cancer Science (2022).
DOI:10.
1111/cas.
15615

In this study, the researchers observed high levels of SETD1A expression in 51.
4% of the human PDAC samples they analyzed, and they also determined that SETD1A may be an independent prognostic factor for disease-free survival, which means that when the patient's tumor is removed, patients with high levels of SETD1A have a shorter duration of disease-free status than patients with low levels of SETD1A.
The results of the study also demonstrate the clinical importance
of SETD1A expression in PDAC.

The researchers then used cultured PDAC cells to analyze how changing the expression of SETD1A affected the behavior of the body's cells, and when they overexpressed levels of SETD1A, the cells' ability to grow and migrate increased; In another group of PDAC cells, the researchers used molecular techniques to interfere with the expression of SETD1A, and then analyzed other genes affected by it.
Using a special technique called RNA sequencing, the researchers analyzed the overall gene expression after knocking down the expression of SETD1A, and found that another gene called RUVBL1 also had lower
expression levels.

Further results showed that SETD1A can methylate histones near the RUVBL1 gene and activate its gene expression, knocking down the expression of RUVBL1 in PDAC cells may produce a biological effect similar to that observed by previous interference with SETD1A, and the results of survival analysis showed that PDAC patients with high levels of SETD1A and RUVBL1 had a lower overall survival rate, which indicated that Its co-expression is an important prognostic biomarker indicating this cancer
.
Taken together, the results of this study provide a deeper understanding of the meaning of SETD1A and RUVBL1 expression in PDAC, as well as key details to help clinicians make critical clinical treatment decisions
for patients experiencing severe disease.
(Biovalley Bioon.
com)

Original source:

Takeshi Ishii,Yoshimitsu Akiyama,Shu Shimada, et al.
 Identification of a novel target of SETD1A histone methyltransferase and the clinical significance in pancreatic cancer, Cancer Science (2022).
DOI: 10.
1111/cas.
15615