Source: Bio Valley Original 2023-08-07 10:43
Scientists from Singapore’s A*STAR Institute and other institutions have revealed how the loss of the gene PBRM1 leads to kidney cancer.
PBRM1 encodes an accessory subunit of the PBAF SWI/SNF chromatin remodeling factor, and inactivation of PBRM1 is the most common event in RCC, however, the effect of PBRM1 loss on chromatin remodeling has not been well studied .Recently, an article published in the international journalNature Cell BiologyIn the research report entitled “PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma”, scientists from Singapore’s A*STAR Institute and other institutions revealed that the gene PBRM1 How the deletion of the gene leads to the development of kidney cancer.
The researchers say that when the PBRM1 gene is inactivated, it leads to the formation of abnormal protein complexes that activate a cancer-promoting pathway called NF-κB. These complexes redistribute proteins throughout the genome, And lead to increased NF-κB activity and expression of genes that promote cancer cell growth. The PBRM1 gene is the second most frequently mutated gene in kidney cancer, but there is currently very limited research on how it affects the development of kidney cancer. In this study, the researchers provided new insights into the mechanism of kidney cancer development, or It is expected to help develop new potential treatments for this disease.
To reveal the molecular mechanism of human renal carcinogenesis induced by the deletion of specific genes.
Image Source:Nature Cell Biology (2023). DOI:10.1038/s41556-023-01122-y
In this study, the researchers compared the differences between normal and diseased proteins to understand their impact on cancer development, and the findings highlight that PBRM1 may serve as a protective mechanism to prevent abnormal activation of NF-κB and maintain the integrity of healthy proteins, they also found that treating kidney cancer with a drug called bortezomib may inhibit the activation of NF-κB and slow tumor growth.
The researcher, Professor Teh Bin Tean, said that in order to better understand the molecular mechanism by which the PBRM1 gene activates cancer-promoting pathways, we have found a potential new way to treat human kidney cancer. These findings provide scientists and clinicians with a new A therapeutic target that may be used to develop improved therapies for all cancers associated with the NF-κB pathway. The inactivation of PBRM1 is a class of genetic alterations caused by altering the structure of DNA in cells. Scientists have been looking for ways to target and treat these alterations to prevent cancer; this study has demonstrated that by controlling and targeting Applying such genetic changes could pave the way for the development of novel therapies that lead to more appropriate treatments for cancer.
In summary, the results of this study indicate that PBRM1 may protect chromatin in somatic cells by inhibiting the tumor-promoting NF-κB target genes abnormally released by the residual PBRM1-deficient PBAF complex. (bio valleyBioon.com）
Original 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
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2023-08-07 02:43:00
