Abstract
Peritoneal metastasis (PM) is a major contributor to poor prognosis in advanced gastric cancer (GC), yet its molecular mechanisms remain insufficiently understood. The results of bioinformatic analysis and clinical sample validation reveal that LncRNA MZF1-AS1 is significantly upregulated in GC tissues, particularly in peritoneal metastases, and is associated with worse overall and post-progression survival. MZF1-AS1 enhances malignant phenotypes and PM of GC cells in vitro and in vivo. Mechanistically, RAB13 is demonstrated as a functional effector of MZF1-AS1 via RNA-seq. MZF1-AS1 enhances RAB13 expression by promoting its mRNA stability, thereby facilitating GC cell proliferation, EMT, migration, invasion, and stemness. Further, RNA pulldown and Mass Spectrometry reveal that MZF1-AS1 directly binds to NSUN2. MZF1-AS1 strengthens the interaction between NSUN2 and RAB13 mRNA, promoting NSUN2-mediated m5C modification and stabilizing RAB13 mRNA. Our findings uncover a novel epi-transcriptomic mechanism by which MZF1-AS1 promotes GC progression via NSUN2-dependent m5C methylation of RAB13 mRNA, offering new insights into PM pathogenesis and highlighting potential therapeutic targets for advanced GC.
Keywords
Gastric cancer
MZF1-AS1
NSUN2
Peritoneal metastasis
RAB13
MeSH 主题词
Humans
Stomach Neoplasms/pathology,genetics,metabolism
Peritoneal Neoplasms/secondary,genetics,metabolism
Mice
Animals
RNA Stability
rab GTP-Binding Proteins/genetics,metabolism
Gene Expression Regulation, Neoplastic
RNA, Long Noncoding/genetics
RNA, Messenger/genetics,metabolism
Cell Proliferation
Mice, Nude
Male
Prognosis
Kruppel-Like Transcription Factors/genetics
Female
Cell Line, Tumor
Mice, Inbred BALB C
Methyltransferases/metabolism,genetics
Cell Movement
化学物质
rab GTP-Binding Proteins
RNA, Long Noncoding
RNA, Messenger
Kruppel-Like Transcription Factors
Methyltransferases
MZF1 protein, human
作者与单位
共 9 位作者，点击展开单位 / ORCID
Zhang Qi
Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
Zhang Ruihong
Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
Liu Luguang
Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Shandong, People's Republic of China.
Shen Ying
Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
Huo Xiaoning
Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
Nan Yanhui
Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
Zhang Xiaoli
Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
Chai Jie
Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Shandong, People's Republic of China.
Hao Jing
ORCID
Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
[email protected].
