METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10
Abstract Objective N6-methyladenosine (m6A) RNA methylation is involved in governing the mechanism of tumor progression. We aimed to excavate the biological role and mechanism of the m6A methyltransferase METTL3 in cholangiocarcinoma (CCA). Methods METTL3 expression was determined by database and ti...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-022-02809-2 |
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| author | Jingli Cai Zheng Cui Jingyi Zhou Bosen Zhang Ruiqi Lu Youcheng Ding Hai Hu |
| author_facet | Jingli Cai Zheng Cui Jingyi Zhou Bosen Zhang Ruiqi Lu Youcheng Ding Hai Hu |
| author_sort | Jingli Cai |
| collection | DOAJ |
| description | Abstract Objective N6-methyladenosine (m6A) RNA methylation is involved in governing the mechanism of tumor progression. We aimed to excavate the biological role and mechanism of the m6A methyltransferase METTL3 in cholangiocarcinoma (CCA). Methods METTL3 expression was determined by database and tissue microarray analyses. The role of METTL3 in CCA was explored by loss- and gain-of-function experiments. The m6A target of METTL3 was detected by RNA sequencing. The role of AKR1B10 in CCA was explored, and the association between METTL3 and AKR1B10 was confirmed by rescue experiments. Result METTL3 expression was upregulated in CCA tissue, and higher METTL3 expression was implicated in poor prognoses in CCA patients. Overexpression of METTL3 facilitated proliferation, migration, invasion, glucose uptake, and lactate production in CCA cells, whereas knockdown of METTL3 had the opposite effects. We further found that METTL3 deficiency inhibited CCA tumor growth in vivo. RNA sequencing and MeRIP-qPCR confirmed that METTL3 enhanced AKR1B10 expression and m6A modification levels. Furthermore, METTL3 directly binds with AKR1B10 at an m6A modification site. A CCA tissue microarray showed that AKR1B10 expression was upregulated in CCA tissue and that silencing AKR1B10 suppressed the malignant phenotype mentioned above in CCA. Notably, knockdown of AKR1B10 rescued the tumor-promoting effects induced by METTL3 overexpression. Conclusion Elevated METTL3 expression promotes tumor growth and glycolysis in CCA through m6A modification of AKR1B10, indicating that METTL3 is a potential target for blocking glycolysis for application in CCA therapy. |
| first_indexed | 2024-04-11T14:24:24Z |
| format | Article |
| id | doaj.art-65ce36a5a0e14b1dac520f1a062d97ca |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-11T14:24:24Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-65ce36a5a0e14b1dac520f1a062d97ca2022-12-22T04:18:56ZengBMCCancer Cell International1475-28672022-12-0122111810.1186/s12935-022-02809-2METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10Jingli Cai0Zheng Cui1Jingyi Zhou2Bosen Zhang3Ruiqi Lu4Youcheng Ding5Hai Hu6Center of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of MedicineDepartment of Ultrasonic Medicine, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of MedicineDepartment of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineCenter of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of MedicineCenter of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of MedicineCenter of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of MedicineCenter of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of MedicineAbstract Objective N6-methyladenosine (m6A) RNA methylation is involved in governing the mechanism of tumor progression. We aimed to excavate the biological role and mechanism of the m6A methyltransferase METTL3 in cholangiocarcinoma (CCA). Methods METTL3 expression was determined by database and tissue microarray analyses. The role of METTL3 in CCA was explored by loss- and gain-of-function experiments. The m6A target of METTL3 was detected by RNA sequencing. The role of AKR1B10 in CCA was explored, and the association between METTL3 and AKR1B10 was confirmed by rescue experiments. Result METTL3 expression was upregulated in CCA tissue, and higher METTL3 expression was implicated in poor prognoses in CCA patients. Overexpression of METTL3 facilitated proliferation, migration, invasion, glucose uptake, and lactate production in CCA cells, whereas knockdown of METTL3 had the opposite effects. We further found that METTL3 deficiency inhibited CCA tumor growth in vivo. RNA sequencing and MeRIP-qPCR confirmed that METTL3 enhanced AKR1B10 expression and m6A modification levels. Furthermore, METTL3 directly binds with AKR1B10 at an m6A modification site. A CCA tissue microarray showed that AKR1B10 expression was upregulated in CCA tissue and that silencing AKR1B10 suppressed the malignant phenotype mentioned above in CCA. Notably, knockdown of AKR1B10 rescued the tumor-promoting effects induced by METTL3 overexpression. Conclusion Elevated METTL3 expression promotes tumor growth and glycolysis in CCA through m6A modification of AKR1B10, indicating that METTL3 is a potential target for blocking glycolysis for application in CCA therapy.https://doi.org/10.1186/s12935-022-02809-2CholangiocarcinomaMETTL3AKR1B10Glycolysis |
| spellingShingle | Jingli Cai Zheng Cui Jingyi Zhou Bosen Zhang Ruiqi Lu Youcheng Ding Hai Hu METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10 Cancer Cell International Cholangiocarcinoma METTL3 AKR1B10 Glycolysis |
| title | METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10 |
| title_full | METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10 |
| title_fullStr | METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10 |
| title_full_unstemmed | METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10 |
| title_short | METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10 |
| title_sort | mettl3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6a modification of akr1b10 |
| topic | Cholangiocarcinoma METTL3 AKR1B10 Glycolysis |
| url | https://doi.org/10.1186/s12935-022-02809-2 |
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