Knockdown of ASF1B inhibits cell proliferation, migration, invasion and cisplatin resistance in gastric cancer through the Myc pathway

Zhang,Zao; Ning,Meiying; Li,Li; Li,Zhuangzhuang; Wang,Yanrong; Zhao,Jing

doi:10.3892/ol.2023.13828

Knockdown of ASF1B inhibits cell proliferation, migration, invasion and cisplatin resistance in gastric cancer through the Myc pathway

Authors:
- Zao Zhang
- Meiying Ning
- Li Li
- Zhuangzhuang Li
- Yanrong Wang
- Jing Zhao
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Affiliations: Department of Pharmacy, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China
Published online on: April 20, 2023 https://doi.org/10.3892/ol.2023.13828
Article Number: 242
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer (GC) is a prevalent malignancy in the digestive system that poses a serious threat to human health. Anti‑silencing function 1B (ASF1B) performs an important role in the progression of numerous tumors; however, its function in GC still requires further elucidation. Using data from The Cancer Genome Atlas, the expression levels of ASF1B in GC tissues were analyzed and a survival curve for high‑ASF1B expression and low‑ASF1B expression groups was plotted using the Kaplan‑Meier method. Reverse transcription‑quantitative PCR was performed to evaluate ASF1B expression in GC tissues and cells. Small interfering RNAs targeting ASF1B were transfected into HGC‑27 and AGS cells to silence ASF1B expression. Cell viability, proliferation, migration, invasion, and apoptosis in HGC‑27 and AGS cells was assessed using cell counting kit‑8 assay, colony formation assay, wound healing assay, Transwell assay and flow cytometry, respectively. The protein changes were assessed using western blotting. Gene Set Enrichment Analysis (GSEA) was used to identify ASF1B related pathways. The results demonstrated that ASF1B expression was increased in GC tissues and cells compared with adjacent healthy tissues and normal cells (GES‑1), and high expression of ASF1B was associated with poor survival outcomes in patients with GC. Silencing ASF1B inhibited cell viability, colony formation, migration, invasion and cisplatin resistance, while also attenuating the apoptotic capability of HGC‑27 and AGS cells. GSEA showed that ASF1B could activate the Myc‑targets‑v1 and Myc‑targets‑v2 pathways. Moreover, silencing ASF1B inhibited the Myc pathway‑related proteins Myc, minichromosome maintenance (MCM)4 and MCM5. Overexpression of Myc reversed the inhibitory effect of ASF1B silencing on AGS cell proliferation, invasion and cisplatin resistance. In conclusion, the results indicate that knockdown of ASF1B may suppress GC cell proliferation, migration and invasion, and promote cell apoptosis and cisplatin sensitivity by modulating the Myc pathway, thereby offering novel possibilities for reversing cisplatin resistance in GC.

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