Letter to editor regarding “piR-36249 and DHX36 together inhibit testicular cancer cells progression by upregulating OAS2”

Several reports describing PIWI-interacting RNAs (piRNAs) in human cancer cells or in the bloodstream are affected by the presence of false positives in piRNA databases. A recent report suggested that piR-36249 regulates testicular cancer progression by engaging with DHX36 to regulate OAS2. However, piR-36249 is a tRNA-Cys 5’ half capable of forming intermolecular G-quadruplexes. It is therefore expected that DHX36, a helicase with high affinity for DNA and RNA G-quadruplexes, was pulled down using piR-36249 mimicking probes. The suggestion of using piR-36249 as a therapeutic target for testicular cancer is therefore questionable, due to the consequences that tRNA inhibition could have on healthy cells.