THADA inhibits autophagy and increases ۵-FU sensitivity in gastric cancer cells via the PI۳K/AKT/mTOR signaling pathway
Publish place: Iranian Journal of Basic Medical Sciences، Vol: 27، Issue: 2
Publish Year: 1403
نوع سند: مقاله ژورنالی
زبان: English
View: 47
This Paper With 8 Page And PDF Format Ready To Download
- Certificate
- من نویسنده این مقاله هستم
استخراج به نرم افزارهای پژوهشی:
شناسه ملی سند علمی:
JR_IJBMS-27-2_009
تاریخ نمایه سازی: 16 دی 1402
Abstract:
Objective(s): ۵-Fluorouracil (۵-FU) is currently the main drug used in chemotherapy for gastric cancer (GC). The main clinical problems of ۵-FU therapy are insensitivity and acquired resistance to ۵-FU. The mechanism of GC cell resistance to ۵-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 ۵-FU adjuvant chemotherapy. Notably, heightened THADA expression in GC cells was associated with the down-regulation of autophagy-related proteins (LC-۳, ATG۱۳, ULK۱, and TFEB). Furthermore, the PI۳K/AKT/mTOR signaling pathway and mTORC۱ 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 mTORC۱ signaling pathway (mLST۸, RHEB, and TSC۲). THADA exhibited inhibitory effects on autophagy and augmented the sensitivity of GC cells to ۵-FU through the PI۳K/AKT/mTOR signaling pathway.Conclusion: The findings suggest that THADA may be involved in the regulatory mechanism of GC cell sensitivity to ۵-FU. Consequently, the detection of THADA in tumor tissues may bring clinical benefits, specifically for ۵-FU-related chemotherapy administered to GC patients with elevated THADA expression.
Keywords:
Authors
Xianke Lin
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Jiajia Pan
Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China
Hammza Hamoudi
Zhejiang University College of Medicine, Hangzhou, China
Jiren Yu
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
مراجع و منابع این Paper:
لیست زیر مراجع و منابع استفاده شده در این Paper را نمایش می دهد. این مراجع به صورت کاملا ماشینی و بر اساس هوش مصنوعی استخراج شده اند و لذا ممکن است دارای اشکالاتی باشند که به مرور زمان دقت استخراج این محتوا افزایش می یابد. مراجعی که مقالات مربوط به آنها در سیویلیکا نمایه شده و پیدا شده اند، به خود Paper لینک شده اند :