Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Knockdown of TRIP13 inhibits gastric cancer stemness and cisplatin resistance by regulating FBXW7/ENO1 axis

Jiayun Liu¹, Che Chen¹, Guannan Wu¹, Xuequan Yao¹, Fukun Liu¹, Shenlin Liu²

For correspondence:- Shenlin Liu Email: liushenlin30207@126.com Tel:+8613951778559

Accepted: 6 January 2024 Published: 29 January 2024

Citation: Liu J, Chen C, Wu G, Yao X, Liu F, Liu S. Knockdown of TRIP13 inhibits gastric cancer stemness and cisplatin resistance by regulating FBXW7/ENO1 axis. Trop J Pharm Res 2024; 23(1):27-35 doi: 10.4314/tjpr.v23i1.4

© 2024 The authors.
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Abstract

Purpose: To explore the role of thyroid hormone receptor interactor 13 (TRIP13) in gastric cancer (GC) and the associated mechanism.

Methods: TRIP13 expression in GC was found in The Cancer Genome Atlas (TCGA) database and si-TRIP13 was transfected in GC cells in order to generate cell lines with low TRIP13 expression. Cell proliferation was determined by colony formation assay, while cell migration and invasion were evaluated by scratch test and Transwell assay, respectively. Sphere formation assay was used to assess cell stemness characteristics whereas half-inhibitory concentration (IC₅₀) value was evaluated by Cell Counting Kit-8 (CCK8). F-box and WD repeat domain containing 7 (FBXW7) and enolase 1 (ENO1) expression were determined by western-blot assay.

Results: TRIP13 was significantly expressed in GC based on TCGA database (p < 0.001) and high expression predicted poor prognosis in GC patients (p < 0.05). Based on the findings of the cell function assay, si-TRIP13 inhibited the proliferation, migration, invasion and stemness of GC cells (p < 0.001) and decreased the IC50 value. Mechanically, knockdown of TRIP13 decreased ENO1 expression level by stabilizing FBXW7.

Conclusion: TRIP13 functions as an oncogene in GC and stimulates growth and stemness via FBXW7/ENO1 pathway in GC. Thus, a potential therapeutic target for the treatment of gastric cancer is provided by this study.

Keywords: TRIP13, Gastric cancer, Cell proliferation, Cell migration, Stemness, Cisplatin resistance