Journal Article Ppublish
PubMed: 40785027 DOI: 10.1111/jcmm.70764
Dysregulated RNA m6A Methylation Contributes to the Metastasis of Gallbladder Cancer Through miR-146a-5p.
J Cell Mol Med 29(15):e70764
Authors: Yuhui Liu, Ruizhi He, Wenjia Wang, Qilong Xia, Di Zhang, Shutao Pan, Min Wang, Qi Zhang, Simiao Xu, Jun Gong, Renyi Qin
Affiliations
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
- Division of Child Healthcare, Department of Pediatrics, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
- Department of Plastic and Cosmetic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, China.
- Department of Endocrinology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Abstract
Gallbladder cancer (GBC) remains a challenging malignancy with a poor prognosis largely due to its highly metastatic nature and lack of effective treatment options. In this study, we investigated the role of N6-methyladenosine (m6A) modification and its regulatory factors, METTL3 and METTL14, in GBC. Our results showed that m6A levels as well as the expression of METTL3 and METTL14 were significantly downregulated in GBC tissues compared to normal gallbladder tissues. In vitro experiments showed that manipulation of METTL3 and METTL14 expression regulated GBC cell migration and invasive ability, and the liver metastasis model of nude mice further demonstrated the involvement of m6A modification in regulating GBC metastasis. Further investigation identified miR-146a-5p as a downstream target regulated by m6A, with tumour-suppressive effects on GBC cell migration and invasion. Overall, our findings provide new insights into the role of m6A modification and its regulation on microRNA in GBC pathogenesis and offer a potential strategy for the treatment of GBC.
MeSH
Cells, Gallbladder, Neoplasms, Cell Biology, Neoplasm Metastasis, Gallbladder Neoplasms, Therapeutics, Tissues, Rna