2. Academic Validation
  3. Oncogenic tRNA-derived fragment tRF-Leu-CAG promotes tumorigenesis of lung cancer via targeting TCEA3 and increasing autophagy

Oncogenic tRNA-derived fragment tRF-Leu-CAG promotes tumorigenesis of lung cancer via targeting TCEA3 and increasing autophagy

  • J Gene Med. 2024 Sep;26(9):e3737. doi: 10.1002/jgm.3737.
Fan Wu 1,  Binshu Chai 1,  Pengfei Qi 1,  Yaqi Han 1,  Zhitao Gu 2,  Wei Pan 1,  Hui Zhang 1,  Xianyi Wang 1,  Xiaomin Liu 1,  Heng Zou 1,  Chen Liang 1,  YanLi Li 1,  Wentao Fang 2,  Zhongliang Ma 1
Affiliations

Affiliations

  • 1 Lab for Noncoding RNA & Cancer, Shanghai University, Shanghai, China.
  • 2 Department of Thoracic Surgery, Shanghai Chest Hospital, Jiaotong University, Shanghai, China.
PMID: 39198937 DOI: 10.1002/jgm.3737
Abstract

Background: Lung Cancer is a prevalent and severe form of malignant tumors worldwide. tRF-Leu-CAG, a recently discovered non-coding single-stranded small RNA derived from transfer RNA, has sparked interest in exploring its biological functions and potential molecular mechanisms in lung Cancer.

Methods: The abundance of tRF-Leu-CAG was measured via quantitative real-time polymerase chain reaction (qRT-PCR) in 96 sets of lung Cancer tissue samples obtained from clinical patients. Subsequently, both in vivo and in vitro experiments were conducted to validate the biological functions of tRF-Leu-CAG in lung Cancer. Furthermore, an exploration of the potential target genes of tRF-Leu-CAG and its association with Autophagy and drug resistance in lung Cancer was undertaken.

Results: Our analysis revealed a significant upregulation of tRF-Leu-CAG in non-small cell lung Cancer (NSCLC) tissues. Additionally, we observed that heightened expression of tRF-Leu-CAG significantly augmented the proliferation and migration of NSCLC cells, facilitated cell cycle progression, and suppressed Apoptosis. Furthermore, we identified transcription elongation factor A3 (TCEA3) as a direct target gene of tRF-Leu-CAG. TCEA3 inhibited the proliferation and migration of NSCLC, and tRF-Leu-CAG promoted the proliferation and migration of NSCLC by mediating the silencing of TCEA3. Moreover, we demonstrated that the augmentation of paclitaxel resistance by tRF-Leu-CAG was contingent on Autophagy. Finally, tRF-Leu-CAG notably accelerated tumor growth and promoted the process of epithelial-mesenchymal transition (EMT) in vivo.

Conclusions: tRF-Leu-CAG promotes NSCLC tumor growth and metastasis by targeting TCEA3 and promotes paclitaxel resistance by enhancing cellular Autophagy. These results provide potentially effective targets and therapeutic options for the clinical treatment of NSCLC.

Keywords

TCEA3; autophagy; non‐small cell lung cancer; paclitaxel resistance; tRF‐Leu‐CAG.

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