tRF-Pro-CGG Suppresses Cell Proliferation and Promotes Apoptosis in Pancreatic Cancer
Jikuan Zhu1, Xudong Zhang2, Tianping Luo2
1Graduate School of Dalian Medical University, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
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.
Insights
tRNA-derived RNA fragment tRF-Pro-CGG acts as a tumor suppressor in pancreatic cancer (PC). Downregulation of tRF-Pro-CGG promotes PC progression, suggesting its potential as a diagnostic biomarker and therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Pancreatic cancer (PC) remains a significant health challenge with limited effective treatments.
- Aberrant expression of non-coding RNAs, including tRNA-derived fragments (tRFs), is implicated in cancer development.
- The specific role of tRF-Pro-CGG in PC pathogenesis is largely unexplored.
Purpose of the Study:
- To investigate the expression profile of tRF-Pro-CGG in pancreatic cancer.
- To elucidate the functional role of tRF-Pro-CGG in PC cell behavior, including proliferation, migration, invasion, and apoptosis.
- To identify the molecular targets and signaling pathways regulated by tRF-Pro-CGG in PC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and next-generation sequencing for expression analysis.
- In vitro functional assays (cell proliferation, colony formation, migration, invasion, apoptosis) in PC cell lines.
- Dual luciferase reporter assays and Western blotting to identify and validate molecular targets and signaling pathways (CSF1, PI3K-AKT).
Main Results:
- tRF-Pro-CGG expression was significantly downregulated in PC tissues and cell lines.
- Overexpression of tRF-Pro-CGG suppressed PC cell proliferation, clonality, migration, and invasion, while inducing apoptosis.
- tRF-Pro-CGG directly targets CSF1 and modulates the PI3K-AKT signaling pathway, impacting key molecules like AKT, P-AKT, and PTEN.
Conclusions:
- tRF-Pro-CGG functions as a tumor suppressor in pancreatic cancer.
- The tumor-suppressive activity is mediated by targeting CSF1 and regulating the PI3K-AKT pathway.
- tRF-Pro-CGG holds promise as a potential diagnostic biomarker and therapeutic target for pancreatic cancer.
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