Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer
Triple negative breast cancer (TNBC) possesses poor prognosis mainly due to development of chemoresistance and lack of effective endocrine or targeted therapies. MiR-491-5p has been found to play a tumor suppressor role in many cancers including breast cancer. However, the precise role of miR-491-5p...
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MDPI AG
2021-09-01
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| author | Wei-Chieh Huang Hsiang-Cheng Chi Shiao-Lin Tung Po-Ming Chen Ya-Chi Shih Yi-Ching Huang Pei-Yi Chu |
| author_facet | Wei-Chieh Huang Hsiang-Cheng Chi Shiao-Lin Tung Po-Ming Chen Ya-Chi Shih Yi-Ching Huang Pei-Yi Chu |
| author_sort | Wei-Chieh Huang |
| collection | DOAJ |
| description | Triple negative breast cancer (TNBC) possesses poor prognosis mainly due to development of chemoresistance and lack of effective endocrine or targeted therapies. MiR-491-5p has been found to play a tumor suppressor role in many cancers including breast cancer. However, the precise role of miR-491-5p in TNBC has never been elucidated. In this study, we reported the novel tumor suppressor function of FOCAD/miR-491-5p in TNBC. High expression of miR-491-5p was found to be associated with better overall survival in breast cancer patients. We found that miR-491-5p could be an intronic microRNA processed form <i>FOCAD</i> gene. We are the first to demonstrate that both miR-491-5p and FOCAD function as tumor suppressors to inhibit cancer stemness, epithelial-mesenchymal transition, drug resistance, cell migration/invasion, and pulmonary metastasis etc. in TNBC. MiR-491-5p was first reported to directly target Rab interacting factor (RABIF) to downregulate RABIF-mediated TNBC cancer stemness, drug resistance, cell invasion, and pulmonary metastasis via matrix metalloproteinase (MMP) signaling. High expression of RABIF was found to be correlated with poor clinical outcomes of breast cancer and TNBC patients. Our data indicated that miR-491-5p and RABIF are potential prognostic biomarkers and targeting the novel FOCAD/miR-491-5p/RABIF/MMP signaling pathway could serve as a promising strategy in TNBC treatment. |
| first_indexed | 2024-03-10T06:39:06Z |
| format | Article |
| id | doaj.art-01a4edd024ca421cad755f14f0de0a79 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2025-02-17T18:30:17Z |
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| series | Cells |
| spelling | doaj.art-01a4edd024ca421cad755f14f0de0a792024-12-12T09:41:01ZengMDPI AGCells2073-44092021-09-011010252410.3390/cells10102524Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast CancerWei-Chieh Huang0Hsiang-Cheng Chi1Shiao-Lin Tung2Po-Ming Chen3Ya-Chi Shih4Yi-Ching Huang5Pei-Yi Chu6Graduate Institute of Integrated Medicine, China Medical University, NO91, Hsueh-Shih Road, Taichung 40402, TaiwanGraduate Institute of Integrated Medicine, China Medical University, NO91, Hsueh-Shih Road, Taichung 40402, TaiwanDepartment of Hematology and Oncology, Ton-Yen General Hospital, Hsinchu County 30210, TaiwanGraduate Institute of Integrated Medicine, China Medical University, NO91, Hsueh-Shih Road, Taichung 40402, TaiwanGraduate Institute of Integrated Medicine, China Medical University, NO91, Hsueh-Shih Road, Taichung 40402, TaiwanGraduate Institute of Integrated Medicine, China Medical University, NO91, Hsueh-Shih Road, Taichung 40402, TaiwanGraduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung 40402, TaiwanTriple negative breast cancer (TNBC) possesses poor prognosis mainly due to development of chemoresistance and lack of effective endocrine or targeted therapies. MiR-491-5p has been found to play a tumor suppressor role in many cancers including breast cancer. However, the precise role of miR-491-5p in TNBC has never been elucidated. In this study, we reported the novel tumor suppressor function of FOCAD/miR-491-5p in TNBC. High expression of miR-491-5p was found to be associated with better overall survival in breast cancer patients. We found that miR-491-5p could be an intronic microRNA processed form <i>FOCAD</i> gene. We are the first to demonstrate that both miR-491-5p and FOCAD function as tumor suppressors to inhibit cancer stemness, epithelial-mesenchymal transition, drug resistance, cell migration/invasion, and pulmonary metastasis etc. in TNBC. MiR-491-5p was first reported to directly target Rab interacting factor (RABIF) to downregulate RABIF-mediated TNBC cancer stemness, drug resistance, cell invasion, and pulmonary metastasis via matrix metalloproteinase (MMP) signaling. High expression of RABIF was found to be correlated with poor clinical outcomes of breast cancer and TNBC patients. Our data indicated that miR-491-5p and RABIF are potential prognostic biomarkers and targeting the novel FOCAD/miR-491-5p/RABIF/MMP signaling pathway could serve as a promising strategy in TNBC treatment.https://www.mdpi.com/2073-4409/10/10/2524TNBCmiR-491-5pFOCADRABIFMMP |
| spellingShingle | Wei-Chieh Huang Hsiang-Cheng Chi Shiao-Lin Tung Po-Ming Chen Ya-Chi Shih Yi-Ching Huang Pei-Yi Chu Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer Cells TNBC miR-491-5p FOCAD RABIF MMP |
| title | Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer |
| title_full | Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer |
| title_fullStr | Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer |
| title_full_unstemmed | Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer |
| title_short | Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer |
| title_sort | identification of the novel tumor suppressor role of focad mir 491 5p to inhibit cancer stemness drug resistance and metastasis via regulating rabif mmp signaling in triple negative breast cancer |
| topic | TNBC miR-491-5p FOCAD RABIF MMP |
| url | https://www.mdpi.com/2073-4409/10/10/2524 |
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