Pan-cancer tRNA-derived fragment CAT1 coordinates RBPMS to stabilize NOTCH2 mRNA to promote tumorigenesis

Transfer RNA-derived fragments (tRFs) are a class of small non-coding regulatory RNAs that are involved in the pathophysiology of many diseases. However, the role of tRFs in cancer progression remains largely elusive. Here, we demonstrate that a pan-cancer 3'-tRF, CAT1 (cancer associated tRF 1), is ubiquitously up -regulated in tumors and associated with poor prognosis of a variety of cancers, including lung cancer. The upregulated CAT1 in cancer cells binds to RNA-binding protein with multiple splicing (RBPMS) and displaces NOTCH2 association from RBPMS, thereby inhibiting the subsequent CCR4-NOT deadenylation-complex-mediated NOTCH2 mRNA decay. The CAT1-enhanced NOTCH2 expression promotes lung cancer cell pro-liferation and metastasis in vitro and in vivo. In addition, plasma CAT1 levels are substantially increased in patients with lung cancer compared to non-cancer control subjects. Our findings reveal an intrinsic connec-tion between cancer-specific upregulation of CAT1 and cancer progression, show the regulation of NOTCH signaling in cancer by a 3'-tRF, and highlight its great clinical potential.

Automated summary

A study found that a tRF called CAT1 is upregulated in various cancers and is associated with poor prognosis. In cancer cells, CAT1 binds to RBPMS and prevents the degradation of NOTCH2, promoting proliferation and metastasis in lung cancer cells. Additionally, plasma levels of CAT1 are significantly increased in patients with lung cancer.