LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4
Abstract Numerous long noncoding RNAs (lncRNAs) are abnormally expressed in breast cancer (BC), but the underlying mechanisms remain large unknown. Here, we aimed to investigate the functions and mechanisms of lncRNA cancer susceptibility candidate 9 (CASC9) in BC. Western blotting and quantitative...
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| Format: | Article |
| Language: | English |
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Wiley
2022-09-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12573 |
| _version_ | 1798002300559556608 |
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| author | Shan‐Ji Fan Ying Cui Yue‐Hua Li Jia‐Chi Xu Ying‐Ying Shen Hong Huang Ze‐Cheng Hu |
| author_facet | Shan‐Ji Fan Ying Cui Yue‐Hua Li Jia‐Chi Xu Ying‐Ying Shen Hong Huang Ze‐Cheng Hu |
| author_sort | Shan‐Ji Fan |
| collection | DOAJ |
| description | Abstract Numerous long noncoding RNAs (lncRNAs) are abnormally expressed in breast cancer (BC), but the underlying mechanisms remain large unknown. Here, we aimed to investigate the functions and mechanisms of lncRNA cancer susceptibility candidate 9 (CASC9) in BC. Western blotting and quantitative real‐time PCR (qRT‐PCR) were performed to assess gene and protein expression, respectively. The proliferative and metastatic abilities of BC cells were tested by cell counting kit‐8 and transwell assays, respectively. The formation of lymphatic vessels was detected by tube formation assay. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were performed to verify molecular interactions. CASC9 was found to be highly expressed in BC tissues and cell lines, and ectopic overexpression was positively associated with tumor volume, TNM stage, and lymph node metastasis. In addition, CASC9 silencing significantly inhibited the proliferation and invasion of BC cells, as well as BC‐associated invasion and formation of lymphatic vessels of human dermal lymphatic endothelial cells. Mechanical studies demonstrated that CASC9 could be transcriptionally activated by STAT3 and elevate SOX4 expression by enhancing the acetylation of its promoter region. Our results illustrated that STAT3‐activated CASC9 served as a tumor‐promoting gene involved in promoting BC invasion and BC‐associated formation of lymphatic vessels by upregulating SOX4 through altering H3K27ac level. This finding elucidated a new underlying network of CASC9 in the metastasis of BC. |
| first_indexed | 2024-04-11T11:49:45Z |
| format | Article |
| id | doaj.art-78a5a281acda4e91bcccc925447b4f25 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-04-11T11:49:45Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-78a5a281acda4e91bcccc925447b4f252022-12-22T04:25:25ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502022-09-0138984885710.1002/kjm2.12573LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4Shan‐Ji Fan0Ying Cui1Yue‐Hua Li2Jia‐Chi Xu3Ying‐Ying Shen4Hong Huang5Ze‐Cheng Hu6The First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaCollege of Chemistry and Materials Science Hengyang Normal University Hengyang Hunan Province ChinaThe First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaThe First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaThe First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaThe First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaThe First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaAbstract Numerous long noncoding RNAs (lncRNAs) are abnormally expressed in breast cancer (BC), but the underlying mechanisms remain large unknown. Here, we aimed to investigate the functions and mechanisms of lncRNA cancer susceptibility candidate 9 (CASC9) in BC. Western blotting and quantitative real‐time PCR (qRT‐PCR) were performed to assess gene and protein expression, respectively. The proliferative and metastatic abilities of BC cells were tested by cell counting kit‐8 and transwell assays, respectively. The formation of lymphatic vessels was detected by tube formation assay. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were performed to verify molecular interactions. CASC9 was found to be highly expressed in BC tissues and cell lines, and ectopic overexpression was positively associated with tumor volume, TNM stage, and lymph node metastasis. In addition, CASC9 silencing significantly inhibited the proliferation and invasion of BC cells, as well as BC‐associated invasion and formation of lymphatic vessels of human dermal lymphatic endothelial cells. Mechanical studies demonstrated that CASC9 could be transcriptionally activated by STAT3 and elevate SOX4 expression by enhancing the acetylation of its promoter region. Our results illustrated that STAT3‐activated CASC9 served as a tumor‐promoting gene involved in promoting BC invasion and BC‐associated formation of lymphatic vessels by upregulating SOX4 through altering H3K27ac level. This finding elucidated a new underlying network of CASC9 in the metastasis of BC.https://doi.org/10.1002/kjm2.12573breast cancerCASC9invasionSOX4STAT3 |
| spellingShingle | Shan‐Ji Fan Ying Cui Yue‐Hua Li Jia‐Chi Xu Ying‐Ying Shen Hong Huang Ze‐Cheng Hu LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4 Kaohsiung Journal of Medical Sciences breast cancer CASC9 invasion SOX4 STAT3 |
| title | LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4 |
| title_full | LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4 |
| title_fullStr | LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4 |
| title_full_unstemmed | LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4 |
| title_short | LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4 |
| title_sort | lncrna casc9 activated by stat3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing h3k27ac activated sox4 |
| topic | breast cancer CASC9 invasion SOX4 STAT3 |
| url | https://doi.org/10.1002/kjm2.12573 |
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