Small but abundant molecules impacting prostate cancer

Prostate cancer is the second-most common cancer in men. A new study from Thomas Jefferson University uncovered a new potential therapeutic target in tiny molecules called tRNA halves.

Transfer RNA (tRNA) are molecules that transport specific protein-building blocks called amino acids to help build full proteins. tRNA halves are small fragments formed when tRNAs are cut in half, often in response to cellular stress or sex hormones, like androgens, which drive prostate cancer. A study from 2015 reported that tRNA halves are highly expressed in prostate cancer.

“Because tRNA halves are so abundant in prostate cancer, we thought they may be doing something important,” says biochemistry researcher and senior author of the study, Yohei Kirino, PhD.

In their new study, Dr. Kirino and his team discovered that tRNA halves can help prostate cancer cells grow. The researchers focused on one particular tRNA half that was especially abundant in the prostate cancer cells they analyzed. They found that this tRNA half acts almost like a switch to turn on more cell growth. The tRNA half can do this by reducing the amount of a protein called p21, which normally serves as a brake to slow down cell growth. When p21 levels drop, cells are free to grow faster and the cancer progresses.

Digging deeper, the team studied how the tRNA half was able to weaken this cellular brake. Under normal circumstances, a protein called YBX1 allows p21 to do its job to repress cell growth. However, when the tRNA half is present, it interferes with YBX1 and as a result, p21 levels go down, releasing the break on cell growth and allowing cancer cells to grow faster.

“tRNA halves are some of the most abundant molecules in prostate cancer cells, yet they are severely understudied,” says Dr. Kirino, a member of Sidney Kimmel Medical College. “Our work shows that these RNA fragments are not simply byproducts of RNA breakdown, but powerful regulators that can influence cancer growth. Understanding their impact could open up new possibilities for therapies in hormone-dependent cancers.”

By Moriah Adde