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Troponin C-1 Activated by E2F1 Accelerates Gastric Cancer Progression via Regulating TGF-β/Smad Signaling

Abstract

Background

Troponin C-1 (TNNC1) has been previously characterized as an oncogenic gene.

Aims

This study aimed to reveal the roles of TNNC1 in gastric cancer and the potential underlying mechanisms.

Methods

TNNC1 siRNAs and TNNC1 overexpression plasmid were used to alter its expression in AGS, MKN45, and HGC-27 cells. CCK-8 assay, colony formation, EdU assay, flow cytometry, transwell assay, and scratch test were conducted to measure the phenotype changes. In vivo effects of TNNC1 silence were confirmed by using a xenograft mouse model. Bioinformatics analysis was conducted to screen out the transcription factor and downstream signaling of TNNC1.

Results

TNNC1 was highly expressed in gastric cancer tissues and cell lines, and its expression was associated with poor prognosis. TNNC1 silence suppressed the proliferation, migration, and invasion of AGS and MKN45 cells. However, TNNC1 silence induced apoptosis by mediating the cleavage of caspase-3 and caspase-9. Overexpression of TNNC1 in HGC-27 cells led to the contrary effects. The anti-tumor effects of TNNC1 silence were also confirmed in a xenograft animal model. E2F1 was validated as an upstream transcription factor of TNNC1. Effects of TNNC1 silence on AGS cell migration and invasion were attenuated by E2F1 overexpression. Besides, TGF-β/Smad was a downstream signaling pathway of TNNC1. The anti-tumor impacts of TNNC1 silence were weaken by SB431542 (a specific inhibitor of TGF-β signaling) while accelerated by TGF-β.

Conclusion

TNNC1 activated by E2F1 functioned as an oncogenic gene through regulating TGF-β/Smad signaling. TNNC1 was suggested as a potential molecular drug target of gastric cancer.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

Authors

Contributions

XZ designed the study; CF and HL performed the research; CL and FL analyzed data; XZ wrote the paper.

Corresponding author

Correspondence to Hui Liu.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

The protocol of this research has been approved by the Ethics Committee of Yantai Affiliated Hospital of Binzhou Medical University. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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All patients have signed written informed consent.

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Cite this article

Fang, C., Zhang, X., Li, C. et al. Troponin C-1 Activated by E2F1 Accelerates Gastric Cancer Progression via Regulating TGF-β/Smad Signaling. Dig Dis Sci 67, 4444–4457 (2022). https://doi.org/10.1007/s10620-021-07287-6

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Keywords

  • Troponin C-1
  • Gastric cancer
  • E2F1
  • TGF-β
  • Smad signaling