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Lin, Xianke, Pan, Jiajia, Hamoudi, Hammza, Yu, Jiren. (1402). THADA inhibits autophagy and increases 5-FU sensitivity in gastric cancer cells via the PI3K/AKT/mTOR signaling pathway. , 27(2), 195-202. doi: 10.22038/ijbms.2023.72055.15668
Xianke Lin; Jiajia Pan; Hammza Hamoudi; Jiren Yu. "THADA inhibits autophagy and increases 5-FU sensitivity in gastric cancer cells via the PI3K/AKT/mTOR signaling pathway". , 27, 2, 1402, 195-202. doi: 10.22038/ijbms.2023.72055.15668
Lin, Xianke, Pan, Jiajia, Hamoudi, Hammza, Yu, Jiren. (1402). 'THADA inhibits autophagy and increases 5-FU sensitivity in gastric cancer cells via the PI3K/AKT/mTOR signaling pathway', , 27(2), pp. 195-202. doi: 10.22038/ijbms.2023.72055.15668
Lin, Xianke, Pan, Jiajia, Hamoudi, Hammza, Yu, Jiren. THADA inhibits autophagy and increases 5-FU sensitivity in gastric cancer cells via the PI3K/AKT/mTOR signaling pathway. , 1402; 27(2): 195-202. doi: 10.22038/ijbms.2023.72055.15668

THADA inhibits autophagy and increases 5-FU sensitivity in gastric cancer cells via the PI3K/AKT/mTOR signaling pathway

Iranian Journal of Basic Medical Sciences
مقاله 9، دوره 27، شماره 2، اردیبهشت 2024، صفحه 195-202    اصل مقاله (788.15 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2023.72055.15668
نویسندگان
Xianke Lin1؛ Jiajia Pan2؛ Hammza Hamoudi3؛ Jiren Yu* 1
1Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
2Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China
3Zhejiang University College of Medicine, Hangzhou, China
چکیده
Objective(s): 5-Fluorouracil (5-FU) is currently the main drug used in chemotherapy for gastric cancer (GC). The main clinical problems of 5-FU therapy are insensitivity and acquired resistance to 5-FU. The mechanism of GC cell resistance to 5-FU is currently unknown.
Materials and Methods: This study employed next-generation sequencing (NGS) to analyze the differentially expressed genes (DEGs) in chemotherapy-sensitive and non-sensitive GC tissues. In addition, a bioinformatics analysis was conducted using the GC dataset of GEO, and further validated and explored through in vitro experiments.
Results: Thyroid adenoma-associated gene (THADA) was highly expressed in GC tissues from chemotherapy-sensitive patients and was an independent prognostic factor in GC patients receiving postoperative 5-FU adjuvant chemotherapy. Notably, heightened THADA expression in GC cells was associated with the down-regulation of autophagy-related proteins (LC-3, ATG13, ULK1, and TFEB). Furthermore, the PI3K/AKT/mTOR signaling pathway and mTORC1 signaling pathway were remarkably increased in patients with elevated THADA expression. THADA expression was associated with mTOR, the core protein of the mTOR signaling pathway, and related proteins involved in regulating the mTORC1 signaling pathway (mLST8, RHEB, and TSC2). THADA exhibited inhibitory effects on autophagy and augmented the sensitivity of GC cells to 5-FU through the PI3K/AKT/mTOR signaling pathway.
Conclusion: The findings suggest that THADA may be involved in the regulatory mechanism of GC cell sensitivity to 5-FU. Consequently, the detection of THADA in tumor tissues may bring clinical benefits, specifically for 5-FU-related chemotherapy administered to GC patients with elevated THADA expression.
کلیدواژه‌ها
Autophagy؛ Fluorouracil؛ Human؛ Stomach Neoplasms THADA protein؛ TOR Serine-Threonine- Kinases
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