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Updated: Jun 28, 2026
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
A novel circSLIT2-encoded SLIT2 isoform suppresses neural invasion in gastric cancer
Xusheng Shen1, Yikai Shen1, Jiang Zeng1
1Gastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
CircRNAs have emerged as critical regulators in various types of cancer. Neural invasion (NI) refers to a process whereby cancer cells infiltrate into the surrounding nerves and has been shown to predict poor prognosis in gastric cancer (GC). Accumulating evidence has suggested that tumor NI is a symbiotic relationship between cancer and nerves, which leads to the growth advantage for both. However, the involvement of circRNAs in the nerve-cancer cell crosstalk remains to be elucidated. In this study, downregulation of circSLIT2 expression was validated in GC tissues, especially in NI-positive GC tissues. Reduced circSLIT2 predicts poor prognosis in GC patients. CircSLIT2 inhibits the migration and neural invasion of GC cells both in vitro and in vivo. Mechanically, a novel peptide (SLIT2-284aa) translated by circSLIT2 was identified. SLIT2-284aa facilitates SLIT2/ROBO1 signaling via binding and inducing the ROBO1 membrane localization. Moreover, SLIT2-284aa enhances the association between ROBO1 and RhoGDI1, which suppresses RhoGDI1 phosphorylation and further reduces the release and activation of RhoA. Our work uncovers a novel circRNA-encoding peptide and a previously unknown SLIT2-284aa/ROBO1/RhoGDI1/RhoA signaling pathway that suppresses cell migration and neural invasion in GC, which provides a new prospect to understand the underlying biological mechanism of the nervous system in GC.
Insights
Circular RNAs (circRNAs) regulate cancer. Downregulated circSLIT2 in gastric cancer (GC) predicts poor prognosis and inhibits neural invasion (NI) by encoding a peptide that suppresses cell migration.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Circular RNAs (circRNAs) are key regulators in cancer.
- Neural invasion (NI) in gastric cancer (GC) correlates with poor prognosis.
- The role of circRNAs in nerve-cancer cell crosstalk in GC is unclear.
Purpose of the Study:
- To investigate the role of circSLIT2 in gastric cancer.
- To elucidate the mechanism of circSLIT2 in regulating neural invasion and cell migration.
- To identify novel pathways involved in nerve-cancer cell crosstalk.
Main Methods:
- Validation of circSLIT2 downregulation in GC tissues.
- In vitro and in vivo experiments to assess circSLIT2's effect on migration and NI.
- Identification and characterization of a novel circRNA-translated peptide (SLIT2-284aa).
- Investigation of the SLIT2-284aa/ROBO1/RhoGDI1/RhoA signaling pathway.
Main Results:
- circSLIT2 expression is downregulated in GC, particularly in NI-positive tumors.
- Reduced circSLIT2 predicts poor prognosis in GC patients.
- circSLIT2 inhibits GC cell migration and NI.
- A novel peptide, SLIT2-284aa, translated by circSLIT2, was identified.
- SLIT2-284aa promotes SLIT2/ROBO1 signaling, enhances ROBO1/RhoGDI1 association, and suppresses RhoA activation.
- A novel SLIT2-284aa/ROBO1/RhoGDI1/RhoA pathway suppressing migration and NI was uncovered.
Conclusions:
- circSLIT2 acts as a tumor suppressor in GC by inhibiting neural invasion and cell migration.
- A novel circRNA-derived peptide, SLIT2-284aa, mediates these effects through the ROBO1/RhoGDI1/RhoA pathway.
- This study reveals a new mechanism of nerve-cancer crosstalk in GC and offers potential therapeutic targets.
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