2. Academic Validation
  3. tRF-3019A/STAU1/BECN1 axis promotes autophagy and malignant progression of colon cancer

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

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: lujiefd005@163.com.
  • 3 Oncology Department, Yueyang People's Hospital, Yueyang Hospital affiliated to Hunan Normal University, Yueyang 414014, China. Electronic address: zcy_0cyz@163.com.
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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