Home / Science / Health /  Research discovers cancer causing-gene controlling variations in prostate cancer

A team of researchers from reputed health institutions of the world discovered a new role for a cancer-causing gene in controlling an important genetic process that underpins genetic variation in prostate cancer. Barts Cancer Institute (BCI) at the Queen Mary University of London, the Italian Institute for Genomic Medicine, and the University of Milan led the research, published in the journal Cell Reports.

The research shows how the gene influences the generation of genetic variants in prostate cancer, which may predict disease relapse and represent new drug targets to improve patient survival.

"Prostate cancer is the commonest male cancer in the world and the lead cause of male cancer-related death. It is very variable in its genetic makeup, which makes diagnosis and treatment tricky, as there is not a one size fits all approach for treating patients. Knowledge of the drivers of genetic variability will help us understand the disease better, and improve treatments," said Dr. Prabhakar Rajan, who was a co-author of the study.

Alternative splicing is the process of rearranging gene segments to generate different combinations of genetic code known as 'splice variants,' which contain the instructions for making proteins. A single gene can code for multiple proteins that are expressed at different levels and serve different functions in the cell thanks to alternative splicing.

The process is critical in normal cells for regulating gene expression and generating genetic and protein diversity. However, alternative splicing is disrupted in many cancer types, including prostate cancer.

The team discovered that the cancer-causing gene FOXA1 is a key regulator of alternative splicing in prostate cancer and may control the generation of splice variants that influence disease relapse and patient survival in this study. In prostate cancer, FOXA1 regulates alternative splicing.

FOXA1 is a pioneer transcription factor, which is a type of protein. Transcription factors can control which genes in our DNA are transcribed into instructions for making proteins within our cells, as well as the rate at which this occurs. It allows different transcription factors to bind to DNA. Changes in FOXA1 have been linked to the onset and progression of prostate cancer.

The team discovered that high levels of FOXA1 limited genetic diversity towards splice variants that have a functional benefit for cancer cells by analyzing alternative splicing in cell line models and primary cases of prostate cancer.

According to the findings, FOXA1 favored splice variants expressed at high levels within the cells and silenced splice variants expressed at low levels, reducing splicing variability in prostate cancer.

"This unique finding has never been shown before for a controller of alternative splicing and may mean that FOXA1 directs prostate cancer cells to act in a particular way that may be detrimental to patients," Dr. Rajan said

Co-senior author Professor Matteo Cereda, Associate Professor at the University of Milan and Group Leader at the Italian Institute for Genomic Medicine, added: "For the first time we show that an early player of transcription regulation is also responsible for the fine-tuning of alternative splicing."Potential new targets for treatment.

The team examined clinical data from over 300 patients with primary prostate cancer from The Cancer Genome Atlas to see if FOXA1-controlled alternative splicing affected patient survival.

Even though high levels of FOXA1 reduced splicing variability, the researchers discovered that FOXA1 increased the inclusion of genetic segments into splice variants, which are strong predictors of prostate cancer recurrence.

Using the cell lines of prostate cancer, the researchers discovered that the inclusion of one specific genetic segment in the splice variant of the FLNA gene, which is controlled by FOXA1, conferred a growth advantage to prostate cancer cells, potentially leading to early disease relapse.

"This study illustrates how we can exploit the power of genomics to make important scientific discoveries about how genetic variability in prostate cancer is controlled. We hope our findings will have a clinical impact by identifying more precise markers of disease recurrence and new potential drug targets," Dr. Ranjan said.

The team is now considering testing whether the splice variants linked to cancer recurrence are useful in predicting disease relapse in reality. They are also conducting experiments to see if targeting these genes could represent new ways to treat prostate cancer.

With Inputs from ANI.

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