miR-506 attenuates methylation of lncRNA MEG3 to inhibit migration and invasion of breast cancer cell lines via targeting SP1 and SP3
Abstract Background Breast cancer has been the first death cause of cancer in women all over the world. Metastasis is believed to be the most important process for treating breast cancer. There is evidence that lncRNA MEG3 functions as a tumor suppressor in breast cancer metastasis. However, upstrea...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-018-0642-8 |
| _version_ | 1818502979312943104 |
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| author | Xin-Xing Wang Guang-Cheng Guo Xue-Ke Qian Dong-Wei Dou Zhe Zhang Xiao-Dong Xu Xin Duan Xin-Hong Pei |
| author_facet | Xin-Xing Wang Guang-Cheng Guo Xue-Ke Qian Dong-Wei Dou Zhe Zhang Xiao-Dong Xu Xin Duan Xin-Hong Pei |
| author_sort | Xin-Xing Wang |
| collection | DOAJ |
| description | Abstract Background Breast cancer has been the first death cause of cancer in women all over the world. Metastasis is believed to be the most important process for treating breast cancer. There is evidence that lncRNA MEG3 functions as a tumor suppressor in breast cancer metastasis. However, upstream regulation of MEG3 in breast cancer remain elusive. Therefore, it is critical to elucidate the underlying mechanism upstream MEG3 to regulate breast cancer metastasis. Methods We employed RT-qPCR and Western blot to examine expression level of miR-506, DNMT1, SP1, SP3 and MEG3. Besides, methylation-specific PCR was used to determine the methylation level of MEG3 promoter. Wound healing assay and transwell invasion assay were utilized to measure migration and invasion ability of breast cancer cells, respectively. Results SP was upregulated while miR-506 and MEG3 were downregulated in breast tumor tissue compared to adjacent normal breast tissues. In addition, we found that miR-506 regulated DNMT1 expression in an SP1/SP3-dependent manner, which reduced methylation level of MEG3 promoter and upregulated MEG3 expression. SP3 knockdown or miR-506 mimic suppressed migration and invasion of MCF-7 and MDA-MB-231 cells whereas overexpression of SP3 compromised miR-506-inhibited migration and invasion. Conclusions Our data reveal a novel axis of miR-506/SP3/SP1/DNMT1/MEG3 in regulating migration and invasion of breast cancer cell lines, which provide rationales for developing effective therapies to treating metastatic breast cancers. |
| first_indexed | 2024-12-10T21:17:36Z |
| format | Article |
| id | doaj.art-0f96867eec0545ed8aeb1886730bc0e0 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-10T21:17:36Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-0f96867eec0545ed8aeb1886730bc0e02022-12-22T01:33:14ZengBMCCancer Cell International1475-28672018-10-0118111110.1186/s12935-018-0642-8miR-506 attenuates methylation of lncRNA MEG3 to inhibit migration and invasion of breast cancer cell lines via targeting SP1 and SP3Xin-Xing Wang0Guang-Cheng Guo1Xue-Ke Qian2Dong-Wei Dou3Zhe Zhang4Xiao-Dong Xu5Xin Duan6Xin-Hong Pei7Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, the First Affiliated Hospital of Zhengzhou UniversityAbstract Background Breast cancer has been the first death cause of cancer in women all over the world. Metastasis is believed to be the most important process for treating breast cancer. There is evidence that lncRNA MEG3 functions as a tumor suppressor in breast cancer metastasis. However, upstream regulation of MEG3 in breast cancer remain elusive. Therefore, it is critical to elucidate the underlying mechanism upstream MEG3 to regulate breast cancer metastasis. Methods We employed RT-qPCR and Western blot to examine expression level of miR-506, DNMT1, SP1, SP3 and MEG3. Besides, methylation-specific PCR was used to determine the methylation level of MEG3 promoter. Wound healing assay and transwell invasion assay were utilized to measure migration and invasion ability of breast cancer cells, respectively. Results SP was upregulated while miR-506 and MEG3 were downregulated in breast tumor tissue compared to adjacent normal breast tissues. In addition, we found that miR-506 regulated DNMT1 expression in an SP1/SP3-dependent manner, which reduced methylation level of MEG3 promoter and upregulated MEG3 expression. SP3 knockdown or miR-506 mimic suppressed migration and invasion of MCF-7 and MDA-MB-231 cells whereas overexpression of SP3 compromised miR-506-inhibited migration and invasion. Conclusions Our data reveal a novel axis of miR-506/SP3/SP1/DNMT1/MEG3 in regulating migration and invasion of breast cancer cell lines, which provide rationales for developing effective therapies to treating metastatic breast cancers.http://link.springer.com/article/10.1186/s12935-018-0642-8Breast cancerMigration and invasionmiR-506SP3DNMT1MEG3 |
| spellingShingle | Xin-Xing Wang Guang-Cheng Guo Xue-Ke Qian Dong-Wei Dou Zhe Zhang Xiao-Dong Xu Xin Duan Xin-Hong Pei miR-506 attenuates methylation of lncRNA MEG3 to inhibit migration and invasion of breast cancer cell lines via targeting SP1 and SP3 Cancer Cell International Breast cancer Migration and invasion miR-506 SP3 DNMT1 MEG3 |
| title | miR-506 attenuates methylation of lncRNA MEG3 to inhibit migration and invasion of breast cancer cell lines via targeting SP1 and SP3 |
| title_full | miR-506 attenuates methylation of lncRNA MEG3 to inhibit migration and invasion of breast cancer cell lines via targeting SP1 and SP3 |
| title_fullStr | miR-506 attenuates methylation of lncRNA MEG3 to inhibit migration and invasion of breast cancer cell lines via targeting SP1 and SP3 |
| title_full_unstemmed | miR-506 attenuates methylation of lncRNA MEG3 to inhibit migration and invasion of breast cancer cell lines via targeting SP1 and SP3 |
| title_short | miR-506 attenuates methylation of lncRNA MEG3 to inhibit migration and invasion of breast cancer cell lines via targeting SP1 and SP3 |
| title_sort | mir 506 attenuates methylation of lncrna meg3 to inhibit migration and invasion of breast cancer cell lines via targeting sp1 and sp3 |
| topic | Breast cancer Migration and invasion miR-506 SP3 DNMT1 MEG3 |
| url | http://link.springer.com/article/10.1186/s12935-018-0642-8 |
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