tRF-Pro-CGG Suppresses Cell Proliferation and Promotes Apoptosis in Pancreatic Cancer

Jikuan Zhu; Xudong Zhang; Tianping Luo; Cailin Xue; Jiadeng Chao; Jun Li; Bei Zhu; Lei Jin; Chunfu Zhu; Xihu Qin

doi:10.1007/s10620-025-08943-x

tRF-Pro-CGG Suppresses Cell Proliferation and Promotes Apoptosis in Pancreatic Cancer

Dig Dis Sci. 2025 Mar 8. doi: 10.1007/s10620-025-08943-x. Online ahead of print.

Authors

Jikuan Zhu¹, Xudong Zhang², Tianping Luo², Cailin Xue², Jiadeng Chao², Jun Li², Bei Zhu², Lei Jin³, Chunfu Zhu², Xihu Qin²

Affiliations

¹ Graduate School of Dalian Medical University, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
² Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Changzhou No.2 People'S Hospital of Nanjing Medical University, Changzhou, 213003, Jiangsu, China.
³ Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Changzhou No.2 People'S Hospital of Nanjing Medical University, Changzhou, 213003, Jiangsu, China. jinlei8016@163.com.

PMID: 40056302
DOI: 10.1007/s10620-025-08943-x

Abstract

Objective: This study aimed to investigate the role of tRNA-derived RNA fragment tRF-Pro-CGG in pancreatic cancer (PC), focusing on its expression levels in PC tissues and cell lines, and its effects on cell proliferation, clonality, migration, invasion, and apoptosis. Additionally, the study explored the potential of tRF-Pro-CGG as a diagnostic biomarker and therapeutic target in PC.

Methods: The expression levels of tRF-Pro-CGG in PC tissues and cell lines were analyzed using next-generation sequencing and quantitative real-time PCR (qRT-PCR). Functional assays, including cell proliferation (CCK-8), colony formation, migration (Transwell), invasion (Matrigel), and apoptosis (flow cytometry), were conducted on PC cell lines (SW1990 and PANC-1) transfected with tRF-Pro-CGG mimic or inhibitor. Dual luciferase reporter assays and Western blotting were used to identify and validate the target gene of tRF-Pro-CGG, CSF1, and its involvement in the PI3K-AKT signaling pathway.

Results: tRF-Pro-CGG was significantly downregulated in PC tissues and cell lines compared to normal tissues and cells. Overexpression of tRF-Pro-CGG in SW1990 cells inhibited cell proliferation, clonality, migration, and invasion, while promoting apoptosis. Conversely, inhibition of tRF-Pro-CGG in PANC-1 cells had the opposite effects. Dual luciferase assays confirmed CSF1 as a direct target of tRF-Pro-CGG, and Western blot analysis showed that tRF-Pro-CGG negatively regulated CSF1 expression. Furthermore, tRF-Pro-CGG was found to modulate the PI3K-AKT signaling pathway, with downstream effects on key molecules such as AKT, P-AKT, and PTEN.

Conclusion: tRF-Pro-CGG acts as a tumor suppressor in pancreatic cancer by inhibiting cell proliferation, migration, invasion, and promoting apoptosis, likely through targeting CSF1 and regulating the PI3K-AKT signaling pathway. These findings suggest that tRF-Pro-CGG could serve as a potential diagnostic biomarker and therapeutic target for pancreatic cancer.

Keywords: Apoptosis; CSF1; Clonality; Diagnostic biomarker; Invasion; Migration; Pancreatic cancer; Proliferation; TRF-pro-CGG.

Abstract

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