Title: Scientists Discover Link Between PBRM1 Gene Loss and Kidney Cancer Development
Date: August 7, 2023
A team of researchers from Singapore’s A*STAR Institute and other institutions have made a groundbreaking discovery on how the loss of the PBRM1 gene contributes to kidney cancer. PBRM1 encodes an accessory subunit of the PBAF SWI/SNF chromatin remodeling factor, and its inactivation is the most common event in renal cell carcinoma (RCC). However, the effects of PBRM1 loss on chromatin remodeling have not been extensively studied until now.
In a recent article published in Nature Cell Biology, the Singaporean scientists shed light on the mechanism behind the gene’s deletion and its connection to kidney cancer development. The researchers found that when the PBRM1 gene is inactivated, it leads to the formation of abnormal protein complexes that activate the NF-κB pathway, a cancer-promoting pathway. These complexes cause a redistribution of proteins throughout the genome, leading to increased NF-κB activity and the expression of genes that promote cancer cell growth.
The PBRM1 gene is the second most frequently mutated gene in kidney cancer; however, there has been limited research on its role in the disease’s development. This study offers new insights into the mechanism of kidney cancer and provides an opportunity to develop potential treatments for the disease.
To understand the molecular mechanism of renal carcinogenesis caused by gene deletions, the researchers compared normal and diseased proteins. Their findings suggest that PBRM1 may act as a protective mechanism against abnormal NF-κB pathway activation and ensure the integrity of healthy proteins. Additionally, the researchers discovered that treating kidney cancer with a drug called bortezomib may inhibit NF-κB activation and slow tumor growth.
Professor Teh Bin Tean, a lead researcher in the study, explained that the findings open up new avenues for treating kidney cancer. By understanding how the PBRM1 gene activates cancer-promoting pathways, scientists and clinicians can develop targeted therapies for all cancers associated with the NF-κB pathway. Inactivation of PBRM1 is a class of genetic alterations caused by changes in DNA structure, and researchers are actively seeking ways to target and treat these alterations to prevent cancer.
In summary, this study uncovers the role of PBRM1 in protecting chromatin in somatic cells by inhibiting the release of tumor-promoting NF-κB target genes. These findings contribute to a better understanding of kidney cancer development and pave the way for the development of novel therapies. With further research and development, this discovery has the potential to lead to more effective treatments for various cancers.
Source:
Yao, X., Hong, J.H., Nargund, A.M. et al. PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma. Nat Cell Biol 25, 765–777 (2023). doi：10.1038/s41556-023-01122-y
Disclaimer: This article is based on the original source mentioned above and does not necessarily reflect the views or opinions of this publication.