QJM : monthly journal of the Association of Physicians · 2026
MAFF drives pancreatic cancer progression through AKR1C1-mediated inhibition of ferroptosis.
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Jiang Xin, Chen Xuyu, Xia Jianlei, Zhou Bengang, Zhang Aiping, Chen Yuanyuan, She Qiang, Li Yaoyao, Ding Yanbing, Zhang Min
Аннотация
BACKGROUND: Pancreatic cancer, a highly aggressive malignancy of the digestive tract, is characterized by an insidious onset, nonspecific early symptoms, early metastatic propensity, and resistance to conventional radiotherapy and chemotherapy. These features contribute to its poor clinical outcomes and dismal prognosis.
AIM: This study aimed to elucidate the molecular mechanisms underlying pancreatic cancer progression, identify clinically actionable diagnostic and therapeutic targets, and ultimately improve patient survival rates and treatment efficacy.
METHODS: Using Enhancer Linking by Methylation/Expression Relationships (ELMER), a computational approach, we identified MAFF as a pivotal transcription factor driving pancreatic cancer progression. The oncogenic role of MAFF was validated through in vitro cellular assays and in vivo xenograft models in nude mice. Transcriptome sequencing and functional experiments further delineated the molecular mechanisms by which MAFF promotes tumorigenesis.
RESULTS: MAFF knockdown significantly suppressed cell proliferation, colony formation, migration, and invasion in AsPC-1 and SUIT-2 cell lines. Bioinformatics analysis and dual-luciferase reporter assays identified AKR1C1 as a downstream effector of MAFF. Mechanistically, MAFF-AKR1C1 axis led to malondialdehyde (MDA) accumulation, elevated lipid reactive oxygen species (ROS), and ferroptosis inhibition, thereby fostering pancreatic cancer progression.
CONCLUSION: Our findings demonstrate that MAFF promotes tumorigenesis by suppressing ferroptosis and nominates MAFF as a promising therapeutic target for pancreatic cancer.
AIM: This study aimed to elucidate the molecular mechanisms underlying pancreatic cancer progression, identify clinically actionable diagnostic and therapeutic targets, and ultimately improve patient survival rates and treatment efficacy.
METHODS: Using Enhancer Linking by Methylation/Expression Relationships (ELMER), a computational approach, we identified MAFF as a pivotal transcription factor driving pancreatic cancer progression. The oncogenic role of MAFF was validated through in vitro cellular assays and in vivo xenograft models in nude mice. Transcriptome sequencing and functional experiments further delineated the molecular mechanisms by which MAFF promotes tumorigenesis.
RESULTS: MAFF knockdown significantly suppressed cell proliferation, colony formation, migration, and invasion in AsPC-1 and SUIT-2 cell lines. Bioinformatics analysis and dual-luciferase reporter assays identified AKR1C1 as a downstream effector of MAFF. Mechanistically, MAFF-AKR1C1 axis led to malondialdehyde (MDA) accumulation, elevated lipid reactive oxygen species (ROS), and ferroptosis inhibition, thereby fostering pancreatic cancer progression.
CONCLUSION: Our findings demonstrate that MAFF promotes tumorigenesis by suppressing ferroptosis and nominates MAFF as a promising therapeutic target for pancreatic cancer.