A group of researchers has discovered a new role for a cancer-causing gene in controlling an important genetic process that underpins genetic variation in Prostate cancer.
Research led by the Barts Cancer Institute (BCI) at Queen Mary University of London, the Italian Institute for Genomic Medicine, and the University of Milan. The findings, published in the journal Cell Reports, reveal how the gene influences the generation of genetic variants in prostate cancer that may… Predicts relapse of disease and represents a new drug Objectives to improve patient survival.
Co-senior author Dr Prabhakar Rajan, Group Chair at BCI and Consultant Urologist at Barts Health NHS Trust, said: “Prostate cancer is the most common male cancer in the world and the leading cause of cancer-related death in males. It is very variable in its genetic makeup, making Diagnosis and treatment is difficult, as there is no one-size-fits-all approach to treating patients.Knowledge of the drivers of genetic variation will help us Understand the disease better, improve treatment. “
Alternative splicing is the process by which parts of genes are shuffled to create different sets of genetic code known as “splice variants,” which provide the instructions needed to make proteins. Through alternative splicing, a single gene can code for many different proteins that are expressed at different levels and have different functions in the cell.
Alternative splicing is an important process for the regulation of gene expression and the generation of genetic and protein diversity within normal cells; However, it is inactivated in many types of cancer, including prostate cancer.
In this study, the team identified that the oncogenic gene FOXA1 is a master regulator of alternative splicing in prostate cancer and may control the generation of splice variants that affect disease relapse and patient survival.
FOXA1 is a type of protein known as a leading transcription factor. Transcription factors can determine which genes in our DNA are transcribed in the instructions used to make proteins within our cells, and how often. As a leading factor, FOXA1 opens DNA for binding by distinct transcription factors. Changes in FOXA1 have been found to drive the initiation and progression of prostate cancer.
By evaluating alternative splicing in cell-line models and primary cases of prostate cancer, the team found that high levels of FOXA1 limited genetic diversity toward splice variants that have a functional benefit to cancer cells. Investigations revealed that FOXA1 preferred splice variants that were present at high intracellular levels and silenced splice variants expressed at low levels, thus reducing splice variation in prostate cancer.
“This unique finding has never been shown before for an alternative splicing controller and may mean that FOXA1 directs prostate cancer cells to act in a particular way that may be harmful to patients,” said Dr. Rajan.
“For the first time we show that an early player in transcriptional regulation is also responsible for fine-tuning alternative splicing,” added co-senior author Professor Matteo Cerida, associate professor at the University of Milan and group leader at the Italian Institute of Genomic Medicine.
To determine whether FOXA1-controlled variant splicing has an impact on patient survival, the team analyzed clinical data from more than 300 primary prostate cancer patients, available via The Cancer Genome Atlas.
Although high levels of FOXA1 reduced splice diversity, the team found that FOXA1 promoted the inclusion of gene segments in splice variants that are strong markers of prostate cancer recurrence. Using prostate cancer cell lines, the team revealed that the inclusion of a specific gene segment in a splice variant of a gene called the FLNA gene, which is controlled by FOXA1, confers a growth advantage on prostate cancer cells, which could lead to early disease relapse. .
Dr. Rajan said: “This study demonstrates how we can harness the power of genomics to make important scientific discoveries about how genetic variation in prostate cancer is controlled. We hope that our findings will have a clinical impact by identifying more precise markers of disease recurrence and new potential drug targets.”
The team now would like to further test whether the splice variants they identified are associated with cancer recurrence is useful in actually predicting disease relapse, and conduct experiments to determine whether targeting these genes could represent new avenues for treating prostate cancer.
This story was published from the news agency feed without modifications to the text. Only the title has changed.