AI Article Synopsis
- N6-methyladenosine (mA) modification is critical for managing ferroptosis-related RNAs, but its role in cholangiocarcinoma (CC) is still unclear.
- Public databases revealed METTL16's overexpression in CC, indicating poor patient prognosis, and it was found to protect cells from ferroptosis by maintaining mitochondrial health and affecting iron and lipid metabolism.
- Mechanistically, METTL16 enhances ATF4 mRNA stability through m6A modification, which helps prevent ferroptosis in CC, suggesting potential therapeutic targets in the condition.
Article Abstract
N6-methyladenosine (mA) modification is the most common post-transcriptional modifications, which is critical for the metabolism of ferroptosis-related RNAs. Yet, the impact of mA modification on ferroptosis in cholangiocarcinoma (CC) is far from clear. Public databases and tissue arrays were applied to explore the clinical relevance of METTL16 in CC. Then, the effects of METTL16 on growth and ferroptosis were studied and . Mechanistically, RNA-sequencing, methylated RNA immunoprecipitation, dual-luciferase reporter assays and RNA stability assays were used to identify the METTL16/ATF4 axis in ferroptosis in CC. Clinically, we find that METTL16 is overexpressed and associated with a poor prognosis in patients with CC. Functionally, METTL16 protects against ferroptosis by maintaining mitochondrial homeostasis, including mitochondrial structure, membrane potential and energy products. It also decreases cellular metabolism of Fe and lipid peroxide, thereby promoting cell growth and . Mechanistically, ATF4 is a novel target of METTL16 and METTL16 enhances the m6A level and expression of ATF4 mRNA by inhibiting its decay, which further prevented ferroptosis in CC via m6A modification. Our findings highlighted the role of METTL16/ATF4 in ferroptosis, which sheds light on potential therapeutic strategies for CC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667817 | PMC |
| http://dx.doi.org/10.7150/ijbs.97886 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
METTL16 suppresses ferroptosis in cholangiocarcinoma by promoting ATF4 via mA modification.
Int J Biol Sci
January 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Article Synopsis
- N6-methyladenosine (mA) modification is critical for managing ferroptosis-related RNAs, but its role in cholangiocarcinoma (CC) is still unclear.
- Public databases revealed METTL16's overexpression in CC, indicating poor patient prognosis, and it was found to protect cells from ferroptosis by maintaining mitochondrial health and affecting iron and lipid metabolism.
- Mechanistically, METTL16 enhances ATF4 mRNA stability through m6A modification, which helps prevent ferroptosis in CC, suggesting potential therapeutic targets in the condition.
ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells.
NPJ Precis Oncol
December 2024
Center of Excellence for Cancer and Inflammation, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Cholangiocarcinoma (CCA) is a bile duct malignancy. Our previous comprehensive analysis showed that ferroptosis-related genes can stratify CCA patients into low-risk and high-risk groups based on survival time. Here, we explored the role of ferroptosis in CCA by analyzing mRNA expression in CCA patients from public databases.
View Article and Find Full Text PDFLiquidambaric acid inhibits cholangiocarcinoma progression by disrupting the STAMBPL1/NRF2 positive feedback loop.
Phytomedicine
December 2024
The Department of Hepato-biliary-pancreatic Surgery, The Institute of Hepatobiliary and Pancreatic Diseases, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, PR China; Changzhou Medical Center, Nanjing Medical University, Changzhou, PR China. Electronic address:
Background: Abnormal antioxidant capacity in cancer cells is intimately linked to tumor aggressiveness. Modulating oxidative stress status and inhibiting ferroptosis represents a novel anticancer therapeutic strategy. STAM Binding Protein Like 1 (STAMBPL1), a deubiquitinase, is implicated in various malignancies, yet its function in inhibiting ferroptosis and therapeutic potential for cholangiocarcinoma (CCA) remains unexplored.
View Article and Find Full Text PDFHypericin mediated photodynamic therapy induces ferroptosis via inhibiting the AKT/mTORC1/GPX4 axis in cholangiocarcinoma.
Transl Oncol
December 2024
Department of Hepatobiliary surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China. Electronic address:
Cholangiocarcinoma remains a challenging primary hepatobiliary malignancy with dismal prognosis. Photodynamic therapy (PDT),a less invasive treatment, has been found to inhibit the proliferation and induce ferroptosis, apoptosis and necrosis in other tumor cells in recent years. Regrettably, the role and exact molecule mechanism of PDT is still incompletely clear in cholangiocarcinoma cells.
View Article and Find Full Text PDFEmerging insights into ferroptosis in cholangiocarcinoma (Review).
Oncol Lett
December 2024
Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong 250002, P.R. China.
Cholangiocarcinoma (CCA) is a malignant tumor that arises within the biliary system, which exhibits a progressively increasing incidence and a poor patient prognosis. A thorough understanding of the molecular pathogenesis that drives the progression of CCA is essential for the development of effective molecular target therapeutic approaches. Ferroptosis is driven by excessive iron accumulation and catalysis, lipid peroxidation and the failure of antioxidant defense systems.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!