LSD1 deficiency in breast cancer cells promotes the formation of pre-metastatic niches
Abstract Lysine-specific demethylase 1 (LSD1), a histone demethylating enzyme, plays a crucial role in cancer metastasis. Studies show LSD1 knockout promotes breast cancer lung metastasis, but it’s unknown if it alters the lung microenvironment for metastasis. In this study, we investigated the effe...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-024-00751-2 |
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| _version_ | 1846165604155785216 |
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| author | Yutong Yao Rui Qian Hanwei Gao Yonghao Dai Yueru Shi Peipei An Benkai Xin Ziyu Liu Nan Zhang Youzhong Wan Yuquan He Xin Hu |
| author_facet | Yutong Yao Rui Qian Hanwei Gao Yonghao Dai Yueru Shi Peipei An Benkai Xin Ziyu Liu Nan Zhang Youzhong Wan Yuquan He Xin Hu |
| author_sort | Yutong Yao |
| collection | DOAJ |
| description | Abstract Lysine-specific demethylase 1 (LSD1), a histone demethylating enzyme, plays a crucial role in cancer metastasis. Studies show LSD1 knockout promotes breast cancer lung metastasis, but it’s unknown if it alters the lung microenvironment for metastasis. In this study, we investigated the effects of exosomes from LSD1-knockdown (LSD1 KD) breast cancer cells on pre-metastatic niche formation. Injecting exosomes from LSD1 KD cells in mice resulted in a substantial increase in lung colonization by breast cancer cells, while treatment with exosomes derived from LSD1 KD cells decreased the expression of the ZO-1 and occludin, leading to increased vascular permeability. The LSD1 KD reduced the expression of circDOCK1, which augmented the levels of miR-1270 in exosomes. And miR-1270 inhibited ZO-1 expression in human endothelial cells, which enhanced their permeability. Our study uncovered a novel mechanism in which the LSD1 promotes the formation of pre-metastatic niches via the regulation of exosomal miRNA. |
| format | Article |
| id | doaj-art-1e3ca4c7a3614bcd93ed84de85c059b3 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-1e3ca4c7a3614bcd93ed84de85c059b32024-11-17T12:07:54ZengNature Portfolionpj Precision Oncology2397-768X2024-11-018111510.1038/s41698-024-00751-2LSD1 deficiency in breast cancer cells promotes the formation of pre-metastatic nichesYutong Yao0Rui Qian1Hanwei Gao2Yonghao Dai3Yueru Shi4Peipei An5Benkai Xin6Ziyu Liu7Nan Zhang8Youzhong Wan9Yuquan He10Xin Hu11Cancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin UniversityCancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin UniversityCancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin UniversityCancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin UniversityCancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin UniversityCancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin UniversityCancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin UniversityCancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin UniversityDepartment of Cardiology, China-Japan Union Hospital of Jilin University, Jilin UniversityCancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin UniversityDepartment of Cardiology, China-Japan Union Hospital of Jilin University, Jilin UniversityDepartment of Cardiology, China-Japan Union Hospital of Jilin University, Jilin UniversityAbstract Lysine-specific demethylase 1 (LSD1), a histone demethylating enzyme, plays a crucial role in cancer metastasis. Studies show LSD1 knockout promotes breast cancer lung metastasis, but it’s unknown if it alters the lung microenvironment for metastasis. In this study, we investigated the effects of exosomes from LSD1-knockdown (LSD1 KD) breast cancer cells on pre-metastatic niche formation. Injecting exosomes from LSD1 KD cells in mice resulted in a substantial increase in lung colonization by breast cancer cells, while treatment with exosomes derived from LSD1 KD cells decreased the expression of the ZO-1 and occludin, leading to increased vascular permeability. The LSD1 KD reduced the expression of circDOCK1, which augmented the levels of miR-1270 in exosomes. And miR-1270 inhibited ZO-1 expression in human endothelial cells, which enhanced their permeability. Our study uncovered a novel mechanism in which the LSD1 promotes the formation of pre-metastatic niches via the regulation of exosomal miRNA.https://doi.org/10.1038/s41698-024-00751-2 |
| spellingShingle | Yutong Yao Rui Qian Hanwei Gao Yonghao Dai Yueru Shi Peipei An Benkai Xin Ziyu Liu Nan Zhang Youzhong Wan Yuquan He Xin Hu LSD1 deficiency in breast cancer cells promotes the formation of pre-metastatic niches npj Precision Oncology |
| title | LSD1 deficiency in breast cancer cells promotes the formation of pre-metastatic niches |
| title_full | LSD1 deficiency in breast cancer cells promotes the formation of pre-metastatic niches |
| title_fullStr | LSD1 deficiency in breast cancer cells promotes the formation of pre-metastatic niches |
| title_full_unstemmed | LSD1 deficiency in breast cancer cells promotes the formation of pre-metastatic niches |
| title_short | LSD1 deficiency in breast cancer cells promotes the formation of pre-metastatic niches |
| title_sort | lsd1 deficiency in breast cancer cells promotes the formation of pre metastatic niches |
| url | https://doi.org/10.1038/s41698-024-00751-2 |
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