NAD(P)-dependent steroid dehydrogenase-like is involved in breast cancer cell growth and metastasis
Abstract Background The cholesterol biosynthesis pathway is typically upregulated in breast cancer. The role of NAD(P)-dependent steroid dehydrogenase-like (NSDHL) gene, which is involved in cholesterol biosynthesis, in breast cancer remains unknown. This study aimed to uncover the role of NSDHL in...
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| Format: | Article |
| Language: | English |
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BMC
2020-05-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-020-06840-2 |
| _version_ | 1831517835338186752 |
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| author | So-Hyun Yoon Hoe Suk Kim Ryong Nam Kim So-Youn Jung Bok Sil Hong Eun Ji Kang Han-Byoel Lee Hyeong-Gon Moon Dong-Young Noh Wonshik Han |
| author_facet | So-Hyun Yoon Hoe Suk Kim Ryong Nam Kim So-Youn Jung Bok Sil Hong Eun Ji Kang Han-Byoel Lee Hyeong-Gon Moon Dong-Young Noh Wonshik Han |
| author_sort | So-Hyun Yoon |
| collection | DOAJ |
| description | Abstract Background The cholesterol biosynthesis pathway is typically upregulated in breast cancer. The role of NAD(P)-dependent steroid dehydrogenase-like (NSDHL) gene, which is involved in cholesterol biosynthesis, in breast cancer remains unknown. This study aimed to uncover the role of NSDHL in the growth and metastasis of breast cancer. Methods After NSDHL knockdown by transfection of short interfering RNA into human breast cancer cell lines (MCF-7, MDA-MB-231 and BT-20) and human breast epithelial cell line (MCF10A), cell proliferation assay, cell cycle analysis, three-dimensional cell culture, clonogenic assay, transwell migration and invasion assays, and wound healing assay were performed. Erlotinib was used as the target drug for epidermal growth factor receptor. Immunodeficient mice (NOD.Cg-Prkdcscid Il2rgtm1wjl /SzJ) were used as orthotropic breast tumor models by injecting them with NSDHL-knockdown MDA-MB-231 cells using lentivirus-carrying NSDHL short hairpin RNA. Clinical data from 3951 breast cancer patients in Gene Expression Omnibus databases were used to investigate the potential prognostic role of NSDHL by survival analysis. Results NSDHL knockdown in BT-20, and MDA-MB-231 resulted in a significant decrease in their viability, colony formation, migration, and invasion abilities (p < 0.05). Total cholesterol levels were observed to be significantly decreased in NSDHL-knockdown BT-20 and MDA-MB-231 (p < 0.0001). NSDHL knockdown significantly increased the rate of erlotinib-induced cell death, especially in MDA-MB-231 (p = 0.01). NSDHL knockdown led to significantly decreased tumor growth and lung metastasis in the MDA-MB-231 xenograft model (p < 0.01). Clinically, high NSDHL expression in tumors of patients with breast cancer was associated with significantly reduced recurrence-free survival (p < 0.0001). Conclusions NSDHL might have a role in promoting breast cancer progression. The usage of NSDHL as a therapeutic target in breast cancer needs to be clarified in further studies. |
| first_indexed | 2024-12-11T23:14:22Z |
| format | Article |
| id | doaj.art-c69cec96926f4ef58e6ce6d444a9667d |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-11T23:14:22Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-c69cec96926f4ef58e6ce6d444a9667d2022-12-22T00:46:36ZengBMCBMC Cancer1471-24072020-05-0120111310.1186/s12885-020-06840-2NAD(P)-dependent steroid dehydrogenase-like is involved in breast cancer cell growth and metastasisSo-Hyun Yoon0Hoe Suk Kim1Ryong Nam Kim2So-Youn Jung3Bok Sil Hong4Eun Ji Kang5Han-Byoel Lee6Hyeong-Gon Moon7Dong-Young Noh8Wonshik Han9Seoul National University College of MedicineBiomedical Research Institute, Seoul National University HospitalDepartment of Surgery, Seoul National University HospitalCenter for Breast Cancer, National Cancer CenterDepartment of Surgery, Seoul National University HospitalCancer Research Institute, Seoul National UniversityDepartment of Surgery, Seoul National University HospitalSeoul National University College of MedicineSeoul National University College of MedicineSeoul National University College of MedicineAbstract Background The cholesterol biosynthesis pathway is typically upregulated in breast cancer. The role of NAD(P)-dependent steroid dehydrogenase-like (NSDHL) gene, which is involved in cholesterol biosynthesis, in breast cancer remains unknown. This study aimed to uncover the role of NSDHL in the growth and metastasis of breast cancer. Methods After NSDHL knockdown by transfection of short interfering RNA into human breast cancer cell lines (MCF-7, MDA-MB-231 and BT-20) and human breast epithelial cell line (MCF10A), cell proliferation assay, cell cycle analysis, three-dimensional cell culture, clonogenic assay, transwell migration and invasion assays, and wound healing assay were performed. Erlotinib was used as the target drug for epidermal growth factor receptor. Immunodeficient mice (NOD.Cg-Prkdcscid Il2rgtm1wjl /SzJ) were used as orthotropic breast tumor models by injecting them with NSDHL-knockdown MDA-MB-231 cells using lentivirus-carrying NSDHL short hairpin RNA. Clinical data from 3951 breast cancer patients in Gene Expression Omnibus databases were used to investigate the potential prognostic role of NSDHL by survival analysis. Results NSDHL knockdown in BT-20, and MDA-MB-231 resulted in a significant decrease in their viability, colony formation, migration, and invasion abilities (p < 0.05). Total cholesterol levels were observed to be significantly decreased in NSDHL-knockdown BT-20 and MDA-MB-231 (p < 0.0001). NSDHL knockdown significantly increased the rate of erlotinib-induced cell death, especially in MDA-MB-231 (p = 0.01). NSDHL knockdown led to significantly decreased tumor growth and lung metastasis in the MDA-MB-231 xenograft model (p < 0.01). Clinically, high NSDHL expression in tumors of patients with breast cancer was associated with significantly reduced recurrence-free survival (p < 0.0001). Conclusions NSDHL might have a role in promoting breast cancer progression. The usage of NSDHL as a therapeutic target in breast cancer needs to be clarified in further studies.http://link.springer.com/article/10.1186/s12885-020-06840-2Breast cancerNSDHLKnockdownProliferationMetastasisCholesterol |
| spellingShingle | So-Hyun Yoon Hoe Suk Kim Ryong Nam Kim So-Youn Jung Bok Sil Hong Eun Ji Kang Han-Byoel Lee Hyeong-Gon Moon Dong-Young Noh Wonshik Han NAD(P)-dependent steroid dehydrogenase-like is involved in breast cancer cell growth and metastasis BMC Cancer Breast cancer NSDHL Knockdown Proliferation Metastasis Cholesterol |
| title | NAD(P)-dependent steroid dehydrogenase-like is involved in breast cancer cell growth and metastasis |
| title_full | NAD(P)-dependent steroid dehydrogenase-like is involved in breast cancer cell growth and metastasis |
| title_fullStr | NAD(P)-dependent steroid dehydrogenase-like is involved in breast cancer cell growth and metastasis |
| title_full_unstemmed | NAD(P)-dependent steroid dehydrogenase-like is involved in breast cancer cell growth and metastasis |
| title_short | NAD(P)-dependent steroid dehydrogenase-like is involved in breast cancer cell growth and metastasis |
| title_sort | nad p dependent steroid dehydrogenase like is involved in breast cancer cell growth and metastasis |
| topic | Breast cancer NSDHL Knockdown Proliferation Metastasis Cholesterol |
| url | http://link.springer.com/article/10.1186/s12885-020-06840-2 |
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