tRF-3019A/STAU1/BECN1 axis promotes autophagy and malignant progression of colon cancer

  • Cell Signal. 2025 Aug:132:111813. doi: 10.1016/j.cellsig.2025.111813.
Xiwei Yuan  1 ,  Wei Li  1 ,  Jingjing Li  1 ,  Wujun Zhang  1 ,  Yue Xiong  1 ,  Han Tang  1 ,  Baozhen Lan  1 ,  Jinye Huang  1 ,  Ye Chen  1 ,  Wei Liu  2 ,  Chuanyi Zhou  3
Affiliations
  • 1. Department of OncologyII, Yueyang People's Hospital, Yueyang Hospital affiliated to Hunan Normal University, Yueyang 414014, China.
  • 2. Pathology Department, Yueyang People's Hospital, Yueyang Hospital affiliated to Hunan Normal University, Yueyang 414014, China. Electronic address: [email protected].
  • 3. Oncology Department, Yueyang People's Hospital, Yueyang Hospital affiliated to Hunan Normal University, Yueyang 414014, China. Electronic address: [email protected].
PMID: 40268078 DOI: 10.1016/j.cellsig.2025.111813
Abstract

Background: Tumor incidence, progression, and metastasis may be linked to the aberrant levels of novel non-coding RNA tRNA-derived fragments (tRFs). Uncertainty surrounds the role and possible mechanism of tRF-3019 A in causing colon Cancer to proceed malignantly.

Methods: By using qRT-PCR, transcription levels of tRF-3019 A were found in colon Cancer cell lines and clinical samples. Locked nucleic acid (LNA)-tRF-3019 A or small molecule mimic was utilized to control the levels of tRF-3019 A in cells, and the CCK8 test was employed to assess the cells' capacity for proliferation. The rate of cell migration and invasiveness were assessed using the Transwell Assay. GFP-LC3B formation was seen using fluorescence microscopy, and autophagy-related protein expression was found using western blot analysis. The interactions between STAU1 and BECN1 and between tRF-3019 A and STAU1 were confirmed by RNA pull-down assay and RNA immunoprecipitation analyses. The mRNA and protein expression of STAU1 and BECN1 were found using qRT-PCR and western blot (WB). A xenograft tumor model was constructed to observe the growth of mouse tumors. qRT-PCR was used to detect the transcription levels of tRF-3019 A, STAU1, and BECN1, while WB was used to detect the expression of STAU1, BECN1, autophagy-related proteins, and epithelial-mesenchymal transition (EMT) -related proteins in tumor tissues.

Results: In colon Cancer tissues and cells, tRF-3019 A was overexpressed, and by triggering Autophagy, it may encourage cell division, migration, and invasion. From a mechanistic perspective, tRF-3019 A competitively bound to the STAU1 protein with BECN1 mRNA, thereby enhancing the stable expression of the autophagy-related protein BECN1. In the model of xenograft tumor mice with knockdown of STAU1, blocking tRF-3019 A led to a substantial decrease in the pace of tumor development, a reduction in the expression of EMT-related proteins and Autophagy, and an inhibition of Autophagy.

Conclusion: tRF-3019A activated tumor cell Autophagy and promoted the malignant progression of colon Cancer by competitively binding to the STAU1 protein with BECN1 mRNA.

Keywords
Autophagy; Colon cancer; STAU1; tRNA-derived fragment.
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