The alternative spray of RNA is like a film editor cutting and reorganizing the scenes of the same images to create different versions of a film. By selecting the scenes to be preserved and which leave aside, the publisher can produce a drama, a comedy or even a thriller – all of the same raw material. Likewise, cells epished in different ways to produce a variety of protein from a single gene, adjusting their function as needed. However, when cancer rewrites the script, this process is wrong, fueling the growth and survival of tumors.
In a recent study reported in the February 15 issue of Nature communicationsJackson Laboratory (JAX) and UCONN health scientists show not only how cancer diverts this splicing and closely regulated RNA rearrangement, but also introduce a potential therapeutic strategy that could slow down or even reduce aggressive and difficult to treat tumors. This discovery could transform the way we treat aggressive cancers, such as triple negative breast cancer and certain brain tumors, where current processing options are limited.
At the heart of this work, led by Olga Anczuków, associate professor at Jax and co-program chief at the Jax Cancer Center designated by the NCI, are tiny genetic elements called poison exons, the “switch” out of nature for protein production. When these exons are included in a RNA message, they trigger its destruction before a protein can be done – preventing harmful cellular activity. In healthy cells, poison exons regulate key protein levels, maintaining genetic machines. But in cancer, this safety mechanism often fails.
Anczuków and his team, including Nathan Leclair, a student graduate of MD / PHD in Uconn Health and the Jackson laboratory who led research, and Mattia Brugiolo, researcher of staff who contributed to her expertise, discovered that cancer cells suppress the exonment of poison in a critical gene Critical gene called Criticism Critical Ten called Criticism Critical Ten Critical Critical Critical Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical Gene Critical gene called Gene called Gene called Gene Criticism Tra2β. As such, levels of Tra2β Proteins increase inside cancer cells, causing tumor proliferation.
In addition, the team has found a correlation between the levels of poison exons and the results of the patients. “We have shown for the first time that low levels of poison exonue in the Tra2β The gene is associated with poor results in many different types of cancer, and in particular aggressive and difficult to treat cancer, “said Anczuków. These include breast cancer, brain tumors, ovarian cancers, skin cancers, leukemia and colorectal cancers, explained Anczuków.
Anczuków, Leclair and Brugiolo then saw if they could increase the inclusion of the poison in the Tra2β Gennic and reactivate the killing switch. They found their response in antissens oligonucleotides (ASOS) – Synthetic RNA fragments which can be designed to increase the inclusion of poison exons in a specific way. When introduced in cancer cells, ASOS has actually overturned the genetic switch, restaurants the natural capacity of the body to degrade excess Tra2β RNA and inhibit tumor progression.
“We have found that ASOS can quickly stimulate the inclusion of poison exons, essentially encouraging the cancer cell to deactivate its own growth signals,” said Leclair. “These poison exons work like a rheostat, quickly adjusting protein levels – and this could make ASOS very precise and effective therapy for aggressive cancers.”
Interesting fact, when the researchers completely deleted Tra2β Proteins using the CRISPR gene edition, tumors have continued to grow – suggesting that RNA targeting rather than protein could be a more effective approach. “It tells us that the RNA containing poison is not only silent Tra2β“Explained Anczuków”. It probably kidnaps other RNA connection proteins, creating an even more toxic environment for cancer cells. “”
Other studies will refine therapies based on ASO and will explore their delivery to tumors. However, the preliminary data suggests that ASOs are very specific and do not interfere with normal cellular function, making promising candidates for future cancer treatments. This research was supported by the National Institutes of Health and the Jax Cancer Center designated by the NCI.
(Tagstotranslate) Cancer; Brain tumor; Breast cancer; Colon cancer; Biology; Biotechnology; Genetic; Cell biology
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