The effect of downregulation of ARL9 expression on the proliferation, metastasis and biological behavior of AGS gastric cancer cell lines

Adv Clin Exp Med. 2025 Jan 8. doi: 10.17219/acem/193399. Online ahead of print.

Abstract

Background: Some ADP ribosylation factors (ARF) and ADP ribosylation factor-like (ARL) family are involved in the regulation of certain cancers, but the role of ADP ribosylation factor-like 9 (ARL9) in gastric tumorigenesis remains elusive.

Objectives: The main aim of this study was to evaluate the ARL9 expression within stomach cancer cells and elucidate its influence on the modulation of cancer cell behavior.

Material and methods: Differential ARL9 protein expression in normal stomach and stomach cancer tissue was ascertained through data sourced from the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN). Quantitative analysis of ARL9 expression in gastric cancer tissue and its association with clinicopathological features was performed using quantitative polymerase chain reaction (qPCR) and western blot analysis (WB). Small interfering RNA (siRNA) was employed to suppress ARL9 protein expression in the human stomach gastric adenocarcinoma human gastric adenocarcinoma cells (AGS) cell line. Assessment of AGS gastric cancer (GC) cell proliferation, invasion and migration was performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and transwell techniques.

Results: The expression of ARL9 protein exhibited a significant upregulation in GC tissue, and showed a close association between tumor dimensions (p < 0.05) and the presence of distant metastases (p < 0.05) among individuals diagnosed with GC. However, no significant link was observed with sex, age and tumor-node-metastasis (TNM) staging in gastric malignancy patients. After the introduction of si-ARL9 in the experimental set, there was a noteworthy decrease in ARL9 protein levels in AGS cells (p < 0.01). In contrast to the control cohort, the restraint of ARL9 expression significantly hampered the growth, mobility and infiltration abilities of the AGS GC cell line (p < 0.01).

Conclusions: The significant correlation of ARL9 with the biological behavior of GC indicates its potentially pivotal role in the pathophysiology of the malignancy.

Keywords: ARL9; SiRNA intervention; cellular growth; gastric carcinoma; metastatic dissemination.