Dysregulated <scp>RNA m6A</scp> Methylation Contributes to the Metastasis of Gallbladder Cancer Through <scp>miR</scp>‐146a‐5p

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.

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Publication Details

Journal
Journal of Cellular and Molecular Medicine
Published
2025-08-01
DOI
https://doi.org/10.1111/jcmm.70764
Citations
1
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
0.81

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article

Dysregulated RNA m6A Methylation Contributes to the Metastasis of Gallbladder Cancer Through miR‐146a‐5p

Simiao Xu, Ruizhi He, Shutao Pan, Jun Gong et al.
1 citations
Journal of Cellular and Molecular Medicine
RNA modifications and cancer
0.81
article

Dysregulated RNA m6A Methylation Contributes to the Metastasis of Gallbladder Cancer Through miR‐146a‐5p

Simiao Xu, Ruizhi He, Shutao Pan, Jun Gong, Qi Zhang, Di Zhang, Wenjia Wang, Qilong Xia, Renyi Qin, Yu-Hui Liu, Min Wang
article en
1 citations

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.

Journal of Cellular and Molecular MedicineVol. 29(15)
Hubei University of Science and Technology (CN), Wuhan Children's Hospital (CN), Tongji Hospital (CN), Huazhong University of Science and Technology (CN)
National Natural Science Foundation of China, Natural Science Foundation of Hubei Province
No poverty
Openalex Percentile: Top 25%
RNA modifications and cancer
0.81
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