Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop
Abstract Background miR-133a-3p has been recently discovered to be down-regulated in various human malignancies, including breast cancer, and reduced miR-133a-3p levels have been significantly associated with breast cancer cell growth and invasion. However, the regulatory mechanisms leading to abnor...
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1400-z |
| _version_ | 1819134267255422976 |
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| author | Wanyue Shi Tingting Tang Xinping Li Siwei Deng Ruiyi Li Yingshan Wang Yifei Wang Tiansong Xia Yanfeng Zhang Ke Zen Liang Jin Yi Pan |
| author_facet | Wanyue Shi Tingting Tang Xinping Li Siwei Deng Ruiyi Li Yingshan Wang Yifei Wang Tiansong Xia Yanfeng Zhang Ke Zen Liang Jin Yi Pan |
| author_sort | Wanyue Shi |
| collection | DOAJ |
| description | Abstract Background miR-133a-3p has been recently discovered to be down-regulated in various human malignancies, including breast cancer, and reduced miR-133a-3p levels have been significantly associated with breast cancer cell growth and invasion. However, the regulatory mechanisms leading to abnormal expression of miR-133a-3p in breast cancer remain obscure. Methods qRT-PCR was applied to detect the expression of miR-133a-3p in breast cancer tissues and cell lines. Bisulfite sequencing was used to detect the degree of methylation of the miR-133a-3p promoter. The effects of miR-133a-3p on breast cancer in vitro were examined by cell proliferation assay, transwell assay, flow cytometry, and western blotting. Bioinformatic analysis, dual-luciferase assay and RIP assay were employed to identify the interaction between miR-133a-3p and MAML1. A xenograft model was used to show the metastasis of breast cancer cells. Results We confirmed that miR-133a-3p was silenced by DNA hypermethylation in breast cancer cell lines and tissues, which predicted poor prognosis in breast cancer patients, and reducing miR-133a-3p expression led to a significant increase in the migration, invasion, proliferation, and stemness of breast cancer cells in vitro. Mastermind-like transcriptional coactivator 1 (MAML1) was confirmed to be a target of miR-133a-3p involved in regulating breast cancer metastasis both in vitro and in vivo. Moreover, a series of investigations indicated that MAML1 initiated a positive feedback loop, which could up-regulate DNA methyltransferase 3A (DNMT3A) to promote hypermethylation of the miR-133a-3p promoter. Conclusion Taken together, our findings revealed a novel miR-133a-3p/MAML1/DNMT3A positive feedback loop in breast cancer cells, which may become a potential therapeutic target for breast cancer. |
| first_indexed | 2024-12-22T10:00:28Z |
| format | Article |
| id | doaj.art-93f53c19e92047d68bed63bf6a4c68de |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-22T10:00:28Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-93f53c19e92047d68bed63bf6a4c68de2022-12-21T18:30:08ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-10-0138112010.1186/s13046-019-1400-zMethylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loopWanyue Shi0Tingting Tang1Xinping Li2Siwei Deng3Ruiyi Li4Yingshan Wang5Yifei Wang6Tiansong Xia7Yanfeng Zhang8Ke Zen9Liang Jin10Yi Pan11State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityDepartment of Breast Surgery, Breast Disease Center of Jiangsu Province, First Affiliated Hospital of Nanjing Medical UniversityState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityJiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing UniversityState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical UniversityAbstract Background miR-133a-3p has been recently discovered to be down-regulated in various human malignancies, including breast cancer, and reduced miR-133a-3p levels have been significantly associated with breast cancer cell growth and invasion. However, the regulatory mechanisms leading to abnormal expression of miR-133a-3p in breast cancer remain obscure. Methods qRT-PCR was applied to detect the expression of miR-133a-3p in breast cancer tissues and cell lines. Bisulfite sequencing was used to detect the degree of methylation of the miR-133a-3p promoter. The effects of miR-133a-3p on breast cancer in vitro were examined by cell proliferation assay, transwell assay, flow cytometry, and western blotting. Bioinformatic analysis, dual-luciferase assay and RIP assay were employed to identify the interaction between miR-133a-3p and MAML1. A xenograft model was used to show the metastasis of breast cancer cells. Results We confirmed that miR-133a-3p was silenced by DNA hypermethylation in breast cancer cell lines and tissues, which predicted poor prognosis in breast cancer patients, and reducing miR-133a-3p expression led to a significant increase in the migration, invasion, proliferation, and stemness of breast cancer cells in vitro. Mastermind-like transcriptional coactivator 1 (MAML1) was confirmed to be a target of miR-133a-3p involved in regulating breast cancer metastasis both in vitro and in vivo. Moreover, a series of investigations indicated that MAML1 initiated a positive feedback loop, which could up-regulate DNA methyltransferase 3A (DNMT3A) to promote hypermethylation of the miR-133a-3p promoter. Conclusion Taken together, our findings revealed a novel miR-133a-3p/MAML1/DNMT3A positive feedback loop in breast cancer cells, which may become a potential therapeutic target for breast cancer.http://link.springer.com/article/10.1186/s13046-019-1400-zDNA methylationmiR-133a-3pBreast cancerMetastasisMAML1DNMT3A |
| spellingShingle | Wanyue Shi Tingting Tang Xinping Li Siwei Deng Ruiyi Li Yingshan Wang Yifei Wang Tiansong Xia Yanfeng Zhang Ke Zen Liang Jin Yi Pan Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop Journal of Experimental & Clinical Cancer Research DNA methylation miR-133a-3p Breast cancer Metastasis MAML1 DNMT3A |
| title | Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop |
| title_full | Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop |
| title_fullStr | Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop |
| title_full_unstemmed | Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop |
| title_short | Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop |
| title_sort | methylation mediated silencing of mir 133a 3p promotes breast cancer cell migration and stemness via mir 133a 3p maml1 dnmt3a positive feedback loop |
| topic | DNA methylation miR-133a-3p Breast cancer Metastasis MAML1 DNMT3A |
| url | http://link.springer.com/article/10.1186/s13046-019-1400-z |
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