METTL14-mediated m6A modification upregulates HOXB13 expression to activate NF-κB and exacerbate cervical cancer progression
Cervical cancer (CC) is one of the common malignant tumors in women, and the incidence rate is located in the second place of female tumors. As a major RNA N6-methyladenosine (m6A) methyltransferase, methyltransferase-like 14 (METTL14) is involved in tumor progression by catalyzing methylation modif...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Molecular & Cellular Oncology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/23723556.2024.2423986 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850248041825566720 |
|---|---|
| author | Qian Li Na Zhao Xuejing Ding Jufen Zhao |
| author_facet | Qian Li Na Zhao Xuejing Ding Jufen Zhao |
| author_sort | Qian Li |
| collection | DOAJ |
| description | Cervical cancer (CC) is one of the common malignant tumors in women, and the incidence rate is located in the second place of female tumors. As a major RNA N6-methyladenosine (m6A) methyltransferase, methyltransferase-like 14 (METTL14) is involved in tumor progression by catalyzing methylation modifications in mRNAs. However, the molecular mechanism of METTL14-mediated m6A modification in CC remains not fully revealed. The expression of METTL14 was detected by RT-qPCR and western blot. Cell function was assayed by cell counting kit-8 (CCK-8) assay and flow cytometry analysis. Methylated RNA immunoprecipitation (MeRIP) was used to confirm the relationship between METTL14 and homeobox B13 (HOXB13). In our study, we found that the level of METTL14 was elevated in CC tissues and cells compared with their controls. The inhibition of METTL14 significantly impaired cell proliferation and the epithelial-mesenchymal transition (EMT) process, while also induced apoptosis in HeLa and C33A cells. Furthermore, our findings indicated that homeobox B13 (HOXB13) was a target of METTL14, which positively regulated the expression of HOXB13 in an m6A-dependent manner. Rescue experiments indicated that overexpression of HOXB13 effectively reversed the tumor suppression induced by METTL14 knockdown. Finally, we confirmed that METTL14-modified HOXB13 exerted an oncogenic effect through activation of the nuclear factor kappa B (NF-κB) pathway. In conclusion, our data demonstrated that the m6A modification of HOXB13, mediated by METTL14, facilitated the advancement of CC through targeting the NF-κB pathway, which may be a potential molecular target for the treatment of CC. |
| format | Article |
| id | doaj-art-0ea1dea6b00e4d4493095d98a99c2920 |
| institution | OA Journals |
| issn | 2372-3556 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Molecular & Cellular Oncology |
| spelling | doaj-art-0ea1dea6b00e4d4493095d98a99c29202025-08-20T01:58:48ZengTaylor & Francis GroupMolecular & Cellular Oncology2372-35562024-12-0111110.1080/23723556.2024.2423986METTL14-mediated m6A modification upregulates HOXB13 expression to activate NF-κB and exacerbate cervical cancer progressionQian Li0Na Zhao1Xuejing Ding2Jufen Zhao3Department of Obstetrics and Gynecology, 926th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Kaiyuan, ChinaDepartment of Obstetrics and Gynecology, 926th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Kaiyuan, ChinaDepartment of Obstetrics and Gynecology, 926th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Kaiyuan, ChinaDepartment of Obstetrics and Gynecology, 926th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Kaiyuan, ChinaCervical cancer (CC) is one of the common malignant tumors in women, and the incidence rate is located in the second place of female tumors. As a major RNA N6-methyladenosine (m6A) methyltransferase, methyltransferase-like 14 (METTL14) is involved in tumor progression by catalyzing methylation modifications in mRNAs. However, the molecular mechanism of METTL14-mediated m6A modification in CC remains not fully revealed. The expression of METTL14 was detected by RT-qPCR and western blot. Cell function was assayed by cell counting kit-8 (CCK-8) assay and flow cytometry analysis. Methylated RNA immunoprecipitation (MeRIP) was used to confirm the relationship between METTL14 and homeobox B13 (HOXB13). In our study, we found that the level of METTL14 was elevated in CC tissues and cells compared with their controls. The inhibition of METTL14 significantly impaired cell proliferation and the epithelial-mesenchymal transition (EMT) process, while also induced apoptosis in HeLa and C33A cells. Furthermore, our findings indicated that homeobox B13 (HOXB13) was a target of METTL14, which positively regulated the expression of HOXB13 in an m6A-dependent manner. Rescue experiments indicated that overexpression of HOXB13 effectively reversed the tumor suppression induced by METTL14 knockdown. Finally, we confirmed that METTL14-modified HOXB13 exerted an oncogenic effect through activation of the nuclear factor kappa B (NF-κB) pathway. In conclusion, our data demonstrated that the m6A modification of HOXB13, mediated by METTL14, facilitated the advancement of CC through targeting the NF-κB pathway, which may be a potential molecular target for the treatment of CC.https://www.tandfonline.com/doi/10.1080/23723556.2024.2423986Cervical cancerN6-methyladenosineMETTL14HOXB13NF-κB |
| spellingShingle | Qian Li Na Zhao Xuejing Ding Jufen Zhao METTL14-mediated m6A modification upregulates HOXB13 expression to activate NF-κB and exacerbate cervical cancer progression Molecular & Cellular Oncology Cervical cancer N6-methyladenosine METTL14 HOXB13 NF-κB |
| title | METTL14-mediated m6A modification upregulates HOXB13 expression to activate NF-κB and exacerbate cervical cancer progression |
| title_full | METTL14-mediated m6A modification upregulates HOXB13 expression to activate NF-κB and exacerbate cervical cancer progression |
| title_fullStr | METTL14-mediated m6A modification upregulates HOXB13 expression to activate NF-κB and exacerbate cervical cancer progression |
| title_full_unstemmed | METTL14-mediated m6A modification upregulates HOXB13 expression to activate NF-κB and exacerbate cervical cancer progression |
| title_short | METTL14-mediated m6A modification upregulates HOXB13 expression to activate NF-κB and exacerbate cervical cancer progression |
| title_sort | mettl14 mediated m6a modification upregulates hoxb13 expression to activate nf κb and exacerbate cervical cancer progression |
| topic | Cervical cancer N6-methyladenosine METTL14 HOXB13 NF-κB |
| url | https://www.tandfonline.com/doi/10.1080/23723556.2024.2423986 |
| work_keys_str_mv | AT qianli mettl14mediatedm6amodificationupregulateshoxb13expressiontoactivatenfkbandexacerbatecervicalcancerprogression AT nazhao mettl14mediatedm6amodificationupregulateshoxb13expressiontoactivatenfkbandexacerbatecervicalcancerprogression AT xuejingding mettl14mediatedm6amodificationupregulateshoxb13expressiontoactivatenfkbandexacerbatecervicalcancerprogression AT jufenzhao mettl14mediatedm6amodificationupregulateshoxb13expressiontoactivatenfkbandexacerbatecervicalcancerprogression |