Related Experiment Video
Updated: Aug 9, 2026
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
MNT inhibits lung adenocarcinoma ferroptosis and chemosensitivity by suppressing SAT1
Guangyin Zhao1, Jiaqi Liang1, Yuchen Zhang1
1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Abstract:
Ferroptosis, a type of iron-dependent non-apoptotic cell death, plays a vital role in both tumor proliferation and resistance to chemotherapy. Here, our study demonstrates that MAX's Next Tango (MNT), by involving itself in the spermidine/spermine N1-acetyltransferase 1 (SAT1)-related ferroptosis pathway, promotes the proliferation of lung adenocarcinoma (LUAD) cells and diminishes their sensitivity to chemotherapy. Initially, an RNA-sequence screen of LUAD cells treated with ferroptosis inducers (FINs) reveals a significant increase in MNT expression, suggesting a potential link between MNT and ferroptosis. Overexpression of MNT in LUAD cells hinders changes associated with ferroptosis. Moreover, the upregulation of MNT promotes cell proliferation and suppresses chemotherapy sensitivity, while the knockdown of MNT has the opposite effect. Through the intersection of ChIP-Seq and ferroptosis-associated gene sets, and validation by qPCR and western blot, SAT1 is identified as a potential target of MNT. Subsequently, we demonstrate that MNT binds to the promoter sequence of SAT1 and suppresses its transcription by ChIP-qPCR and dual luciferase assays. Restoration of SAT1 levels antagonizes the efficacy of MNT to inhibit ferroptosis and chemosensitivity and promote cell growth in vitro as well as in vivo. In the clinical context, MNT expression is elevated in LUAD and is inversely connected with SAT1 expression. High MNT expression is also associated with poor patient survival. Our research reveals that MNT inhibits ferroptosis, and impairing chemotherapy effectiveness of LUAD.
Insights
MAX's Next Tango (MNT) promotes lung adenocarcinoma growth and chemotherapy resistance by inhibiting ferroptosis. MNT targets SAT1, suppressing its expression and hindering cell death pathways crucial for cancer treatment.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Ferroptosis, an iron-dependent cell death, is implicated in tumor growth and chemotherapy resistance.
- Understanding the molecular mechanisms regulating ferroptosis is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the role of MAX's Next Tango (MNT) in ferroptosis and its impact on lung adenocarcinoma (LUAD) proliferation and chemotherapy sensitivity.
- To elucidate the molecular pathway through which MNT influences ferroptosis.
Main Methods:
- RNA-sequence screening of LUAD cells treated with ferroptosis inducers.
- Overexpression and knockdown studies of MNT in LUAD cells.
- Chromatin immunoprecipitation sequencing (ChIP-Seq), qPCR, western blot, and dual luciferase assays to identify and validate MNT targets.
- In vitro and in vivo experiments to assess MNT's functional effects.
Main Results:
- MNT expression is significantly upregulated in LUAD cells treated with ferroptosis inducers.
- MNT overexpression promotes LUAD cell proliferation and reduces chemotherapy sensitivity by inhibiting ferroptosis.
- SAT1 is identified as a direct transcriptional target of MNT, with MNT suppressing SAT1 promoter activity.
- Elevated MNT expression in clinical LUAD samples correlates with poor patient survival and inversely with SAT1 expression.
Conclusions:
- MNT plays a critical role in promoting LUAD progression by inhibiting ferroptosis.
- MNT's mechanism involves the suppression of SAT1, leading to reduced ferroptosis and impaired chemotherapy effectiveness.
- MNT represents a potential therapeutic target for overcoming chemotherapy resistance in lung adenocarcinoma.
More Related Videos
Related Concept Videos
01:23Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...
01:24Antiasthma Drugs: Methylxanthines
Theophylline is thought to inhibit phosphodiesterase enzymes, increasing intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). This rise in cAMP and cGMP concentrations stimulates cardiac function,...
01:20Antiasthma Drugs: Muscarinic Receptor Antagonists
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
01:28Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists