Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601
Abstract Background Breast cancer (BC) is a common malignancy worldwide. It has been reported that long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) is abnormally expressed in BC. However, the role of HOTAIR in the malignancy of BC is worth further discussion. This study aims to cla...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-07-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01410-9 |
| _version_ | 1818844411999551488 |
|---|---|
| author | Yuanyuan Wang Guoliang Gong Jingyun Xu Yuanxin Zhang Shenggui Wu Shaohong Wang |
| author_facet | Yuanyuan Wang Guoliang Gong Jingyun Xu Yuanxin Zhang Shenggui Wu Shaohong Wang |
| author_sort | Yuanyuan Wang |
| collection | DOAJ |
| description | Abstract Background Breast cancer (BC) is a common malignancy worldwide. It has been reported that long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) is abnormally expressed in BC. However, the role of HOTAIR in the malignancy of BC is worth further discussion. This study aims to clarify the function and molecular mechanism of HOTAIR in BC. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of HOTAIR, microRNA (miR)-601 and zinc finger E-box binding homeobox 1 (ZEB1). Cell counting kit-8 (CCK-8) and transwell assay were used to detect the proliferation, migration and invasion of cells. Further, the protein levels of AKT, phosphorylated-AKT (p-AKT), ZEB1 and Ki-67 were confirmed by western blot (WB) assay. Moreover, dual-luciferase reporter assay was applied to examine the targeting relationship between HOTAIR and miR-601 or miR-601 and ZEB1. In addition, animal experiments were conducted to verify the effect of HOTAIR on BC tumor growth in vivo. Results HOTAIR was upregulated in BC tissues and cells, and its knockdown suppressed the proliferation, migration, invasion and the activity of AKT signaling pathway of BC cells. HOTAIR could serve as a sponge of miR-601. Further experiments revealed that miR-601 inhibitor could reverse the inhibition effect of HOTAIR silencing on the progression of BC. Meanwhile, ZEB1 was a target of miR-601, and its overexpression could invert the suppression effect of miR-601 overexpression on the progression of BC. Additionally, ZEB1 expression was regulated by HOTAIR and miR-601. Furthermore, interference of HOTAIR could attenuate BC tumor growth in vivo. Conclusion In short, this study demonstrated that HOTAIR promoted the proliferation, migration, invasion of BC through regulating the miR-601/ZEB1 axis, which provided a theoretical basis for the research on lncRNA-directed therapeutics in BC. |
| first_indexed | 2024-12-19T05:13:21Z |
| format | Article |
| id | doaj.art-5fa21ce44f114ec58b27f9161508b3c4 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-19T05:13:21Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-5fa21ce44f114ec58b27f9161508b3c42022-12-21T20:34:44ZengBMCCancer Cell International1475-28672020-07-0120111310.1186/s12935-020-01410-9Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601Yuanyuan Wang0Guoliang Gong1Jingyun Xu2Yuanxin Zhang3Shenggui Wu4Shaohong Wang5Department of Pathology, Shantou Central Hospital and Affiliated Shantou Hospital of Sun Yat-Sen UniversityDepartment of Pathology, The First Affiliated Hospital of Shantou University Medical CollegeDepartment of Pathology, The First Affiliated Hospital of Shantou University Medical CollegeDepartment of Pathology, Chaonan Minsheng Hospital of ShantouDepartment of Pathology, Chaonan Minsheng Hospital of ShantouDepartment of Pathology, Shantou Central Hospital and Affiliated Shantou Hospital of Sun Yat-Sen UniversityAbstract Background Breast cancer (BC) is a common malignancy worldwide. It has been reported that long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) is abnormally expressed in BC. However, the role of HOTAIR in the malignancy of BC is worth further discussion. This study aims to clarify the function and molecular mechanism of HOTAIR in BC. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of HOTAIR, microRNA (miR)-601 and zinc finger E-box binding homeobox 1 (ZEB1). Cell counting kit-8 (CCK-8) and transwell assay were used to detect the proliferation, migration and invasion of cells. Further, the protein levels of AKT, phosphorylated-AKT (p-AKT), ZEB1 and Ki-67 were confirmed by western blot (WB) assay. Moreover, dual-luciferase reporter assay was applied to examine the targeting relationship between HOTAIR and miR-601 or miR-601 and ZEB1. In addition, animal experiments were conducted to verify the effect of HOTAIR on BC tumor growth in vivo. Results HOTAIR was upregulated in BC tissues and cells, and its knockdown suppressed the proliferation, migration, invasion and the activity of AKT signaling pathway of BC cells. HOTAIR could serve as a sponge of miR-601. Further experiments revealed that miR-601 inhibitor could reverse the inhibition effect of HOTAIR silencing on the progression of BC. Meanwhile, ZEB1 was a target of miR-601, and its overexpression could invert the suppression effect of miR-601 overexpression on the progression of BC. Additionally, ZEB1 expression was regulated by HOTAIR and miR-601. Furthermore, interference of HOTAIR could attenuate BC tumor growth in vivo. Conclusion In short, this study demonstrated that HOTAIR promoted the proliferation, migration, invasion of BC through regulating the miR-601/ZEB1 axis, which provided a theoretical basis for the research on lncRNA-directed therapeutics in BC.http://link.springer.com/article/10.1186/s12935-020-01410-9BCHOTAIRmiR-601ZEB1AKT signaling pathway |
| spellingShingle | Yuanyuan Wang Guoliang Gong Jingyun Xu Yuanxin Zhang Shenggui Wu Shaohong Wang Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601 Cancer Cell International BC HOTAIR miR-601 ZEB1 AKT signaling pathway |
| title | Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601 |
| title_full | Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601 |
| title_fullStr | Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601 |
| title_full_unstemmed | Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601 |
| title_short | Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601 |
| title_sort | long noncoding rna hotair promotes breast cancer development by targeting zeb1 via sponging mir 601 |
| topic | BC HOTAIR miR-601 ZEB1 AKT signaling pathway |
| url | http://link.springer.com/article/10.1186/s12935-020-01410-9 |
| work_keys_str_mv | AT yuanyuanwang longnoncodingrnahotairpromotesbreastcancerdevelopmentbytargetingzeb1viaspongingmir601 AT guolianggong longnoncodingrnahotairpromotesbreastcancerdevelopmentbytargetingzeb1viaspongingmir601 AT jingyunxu longnoncodingrnahotairpromotesbreastcancerdevelopmentbytargetingzeb1viaspongingmir601 AT yuanxinzhang longnoncodingrnahotairpromotesbreastcancerdevelopmentbytargetingzeb1viaspongingmir601 AT shengguiwu longnoncodingrnahotairpromotesbreastcancerdevelopmentbytargetingzeb1viaspongingmir601 AT shaohongwang longnoncodingrnahotairpromotesbreastcancerdevelopmentbytargetingzeb1viaspongingmir601 |