The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancer
Infection with high-risk human papillomavirus (HPV), for example, with types 16 and 18, is closely associated with cervical cancer development, which continues to threaten women’s health globally. Although HPV oncogenes have been recognized as the main cause of transformation of normal cervical epit...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Cancer Biology & Therapy |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15384047.2023.2249174 |
| _version_ | 1797404038044581888 |
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| author | Suzhen Wu Lili Liu Huanying Xu Qiaoling Zhu Minhua Tan |
| author_facet | Suzhen Wu Lili Liu Huanying Xu Qiaoling Zhu Minhua Tan |
| author_sort | Suzhen Wu |
| collection | DOAJ |
| description | Infection with high-risk human papillomavirus (HPV), for example, with types 16 and 18, is closely associated with cervical cancer development, which continues to threaten women’s health globally. Although HPV oncogenes have been recognized as the main cause of transformation of normal cervical epithelial cells, non-coding RNA could also be involved in the initiation and promotion of cervical cancer development. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-documented long non-coding RNA (lncRNA), has been previously reported to exert roles in HPV-positive cervical cancer; however, the detailed underlying mechanism has yet to be investigated. In the present study, high expression levels of MALAT1 in HPV-Positive Cervical Cancer cells were confirmed, and silencing MALAT1 resulted in decreased rates of cell proliferation, migration, and invasion, both in vitro and in a zebrafish xenograft tumor model. Moreover, the results obtained showed that silencing MALAT1 led to down-regulation of the N6-methyladenosine (m6A) demethylase ALKBH5 via regulating miR-141-3p expression, which caused a decrease in the expression levels of matrix metalloproteinase 2 (MMP2) and MMP9 expression, thereby suppressing cell migration and invasion. Taken together, the results obtained have suggested that the MALAT-ALKBH5 signaling axis may be activated in HPV-positive cervical cancer cells, which could contribute to cell proliferation and metastasis through the regulation of key genes, such as MMP2 or MMP9. The findings of the present study should both help to improve our understanding of the underlying tumorigenic mechanisms of HPV-positive cervical cancer and be of further use in the development of potential therapeutic drugs. |
| first_indexed | 2024-03-09T02:47:16Z |
| format | Article |
| id | doaj.art-5139502805fc4161b1273fd297bd8d4e |
| institution | Directory Open Access Journal |
| issn | 1538-4047 1555-8576 |
| language | English |
| last_indexed | 2024-03-09T02:47:16Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj.art-5139502805fc4161b1273fd297bd8d4e2023-12-05T15:58:14ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762023-12-0124110.1080/15384047.2023.22491742249174The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancerSuzhen Wu0Lili Liu1Huanying Xu2Qiaoling Zhu3Minhua Tan4Foshan Fosun Chancheng HospitalFoshan Fosun Chancheng HospitalFoshan Fosun Chancheng HospitalFoshan Fosun Chancheng HospitalFoshan Fosun Chancheng HospitalInfection with high-risk human papillomavirus (HPV), for example, with types 16 and 18, is closely associated with cervical cancer development, which continues to threaten women’s health globally. Although HPV oncogenes have been recognized as the main cause of transformation of normal cervical epithelial cells, non-coding RNA could also be involved in the initiation and promotion of cervical cancer development. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-documented long non-coding RNA (lncRNA), has been previously reported to exert roles in HPV-positive cervical cancer; however, the detailed underlying mechanism has yet to be investigated. In the present study, high expression levels of MALAT1 in HPV-Positive Cervical Cancer cells were confirmed, and silencing MALAT1 resulted in decreased rates of cell proliferation, migration, and invasion, both in vitro and in a zebrafish xenograft tumor model. Moreover, the results obtained showed that silencing MALAT1 led to down-regulation of the N6-methyladenosine (m6A) demethylase ALKBH5 via regulating miR-141-3p expression, which caused a decrease in the expression levels of matrix metalloproteinase 2 (MMP2) and MMP9 expression, thereby suppressing cell migration and invasion. Taken together, the results obtained have suggested that the MALAT-ALKBH5 signaling axis may be activated in HPV-positive cervical cancer cells, which could contribute to cell proliferation and metastasis through the regulation of key genes, such as MMP2 or MMP9. The findings of the present study should both help to improve our understanding of the underlying tumorigenic mechanisms of HPV-positive cervical cancer and be of further use in the development of potential therapeutic drugs.http://dx.doi.org/10.1080/15384047.2023.2249174malat1alkbh5proliferationmigrationinvasionhpv-positive cervical cancer |
| spellingShingle | Suzhen Wu Lili Liu Huanying Xu Qiaoling Zhu Minhua Tan The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancer Cancer Biology & Therapy malat1 alkbh5 proliferation migration invasion hpv-positive cervical cancer |
| title | The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancer |
| title_full | The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancer |
| title_fullStr | The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancer |
| title_full_unstemmed | The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancer |
| title_short | The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancer |
| title_sort | involvement of malat1 alkbh5 signaling axis into proliferation and metastasis of human papillomavirus positive cervical cancer |
| topic | malat1 alkbh5 proliferation migration invasion hpv-positive cervical cancer |
| url | http://dx.doi.org/10.1080/15384047.2023.2249174 |
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