tRF3008A suppresses the progression and metastasis of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner

Journal of Experimental & Clinical Cancer Research

Edward Shen¹  Hong Shen²  Cao Guo²  Le Gao²  Shan Zeng²  Yinghui Peng²  Jie Long²  Shanshan Liu²  Min He²  Qiaoqiao Huang²  Changjing Cai²  Xinwen Wang²  Yihong Chen²  Ying Han²  Jian Yu³ 

[1] Department of Life Science, McMaster University;Department of Oncology, Xiangya Hospital, Central South University;Department of Pathology, University of Pittsburgh School of Medicine;

关键词: tRNA-derived fragments (tRFs);    tRF3008A;    FOXK1;    AGO;    Colorectal cancer;   

DOI  :  10.1186/s13046-021-02190-4

来源: DOAJ

【 摘 要 】

Abstract Background tRNA-derived fragments (tRFs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of tRFs to colorectal cancer (CRC) remain largely unknown. Methods tRF3008A (a tRFRNA derived from tRNAVal) was identified by RNA sequencing and validated by quantitative reverse transcription PCR. The role of tRF3008A in CRC progression was assessed both in vitro and in vivo, and its downstream target genes were identified and validated in CRC cells. RNA pull-down with mass spectrometry and AGO-RIP were used to confirm the interaction of tRF3008A and AGO proteins. The clinical implications of tRF3008A were assessed in CRC tissues and blood samples. Results The expression of tRF3008A was reduced in colorectal cancer, and its reduction was significantly correlated with advanced and metastatic disease in CRC. Patients with low tRF3008A expression showed significantly shorter DFS, and multivariate analysis identified tRF3008A as an independent prognostic biomarker in CRC. Functionally, tRF3008A inhibits the proliferation and migration of CRC in vivo and in vitro by repressing endogenous FOXK1, a positive regulator of the Wnt/β-catenin pathway. Mechanistically, tRF3008A binds to AGO proteins as a guide to destabilize oncogenic FOXK1 transcript. Conclusions tRF3008A suppresses the metastasis and progression of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner.

【 授权许可】

Unknown