EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling
Abstract CircBRWD3 is a newly discovered circRNA, and its potential function has not been probed. Here, we aimed to molecularly dissect the role of circBRWD3 in the tumorigenesis and progression of breast cancer (BC). qRT-PCR analysis revealed that circBRWD3 expression was dramatically upregulated i...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-10200-7 |
| _version_ | 1811190424578031616 |
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| author | Xianguo Meng Wei Li Ziqi Meng Yan Li |
| author_facet | Xianguo Meng Wei Li Ziqi Meng Yan Li |
| author_sort | Xianguo Meng |
| collection | DOAJ |
| description | Abstract CircBRWD3 is a newly discovered circRNA, and its potential function has not been probed. Here, we aimed to molecularly dissect the role of circBRWD3 in the tumorigenesis and progression of breast cancer (BC). qRT-PCR analysis revealed that circBRWD3 expression was dramatically upregulated in BC tissues, a feature that was positively correlated with the poor prognosis of patients with BC. CircBRWD3 knockdown repressed cell proliferation and metastasis, while promoting cell apoptosis in vitro. Consistently, an in vivo circBRWD3 deficiency model exhibited suppressed tumor metastasis and oncogenesis. On the other hand, circBRWD3 overexpression promoted cancer cell activity and tumorigenesis. Further, mechanistic studies elucidated that circBRWD3 sponged both miR-142-3p and miR-142-5p to modulate RAC1 expression, which subsequently activated the RAC1/PAK1 signaling to facilitate the tumorigenesis and progression of BC. Moreover, we discovered that EIF4A3 facilitated circBRWD3 expression by targeting the upstream of BRWD3 pre-mRNA. In conclusion, our study reveals that circBRWD3 facilitates BC tumorigenesis by regulating the circBRWD3/miR-142-3p_miR-142-5p /RAC1/PAK1 axis. In addition, circBRWD3 expression is positively regulated by an RNA-binding protein, EIFA3. Our results provide valuable scientific data for early diagnosis and therapy for breast cancer patients. |
| first_indexed | 2024-04-11T14:50:57Z |
| format | Article |
| id | doaj.art-b278975a8b244dc792718a464c0a5900 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-11T14:50:57Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-b278975a8b244dc792718a464c0a59002022-12-22T04:17:28ZengBMCBMC Cancer1471-24072022-11-0122111410.1186/s12885-022-10200-7EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signalingXianguo Meng0Wei Li1Ziqi Meng2Yan Li3College of Sports Medicines and Rehabilitation, Shandong First Medical UniversityCollege of Sports Medicines and Rehabilitation, Shandong First Medical UniversityAccounting Institute, Shandong University of Finance and EconomicsCollege of Sports Medicines and Rehabilitation, Shandong First Medical UniversityAbstract CircBRWD3 is a newly discovered circRNA, and its potential function has not been probed. Here, we aimed to molecularly dissect the role of circBRWD3 in the tumorigenesis and progression of breast cancer (BC). qRT-PCR analysis revealed that circBRWD3 expression was dramatically upregulated in BC tissues, a feature that was positively correlated with the poor prognosis of patients with BC. CircBRWD3 knockdown repressed cell proliferation and metastasis, while promoting cell apoptosis in vitro. Consistently, an in vivo circBRWD3 deficiency model exhibited suppressed tumor metastasis and oncogenesis. On the other hand, circBRWD3 overexpression promoted cancer cell activity and tumorigenesis. Further, mechanistic studies elucidated that circBRWD3 sponged both miR-142-3p and miR-142-5p to modulate RAC1 expression, which subsequently activated the RAC1/PAK1 signaling to facilitate the tumorigenesis and progression of BC. Moreover, we discovered that EIF4A3 facilitated circBRWD3 expression by targeting the upstream of BRWD3 pre-mRNA. In conclusion, our study reveals that circBRWD3 facilitates BC tumorigenesis by regulating the circBRWD3/miR-142-3p_miR-142-5p /RAC1/PAK1 axis. In addition, circBRWD3 expression is positively regulated by an RNA-binding protein, EIFA3. Our results provide valuable scientific data for early diagnosis and therapy for breast cancer patients.https://doi.org/10.1186/s12885-022-10200-7Breast cancerEIF4A3CircBRWD3MiR-142-3pMiR-142-5pRAC1-PAK1 signaling |
| spellingShingle | Xianguo Meng Wei Li Ziqi Meng Yan Li EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling BMC Cancer Breast cancer EIF4A3 CircBRWD3 MiR-142-3p MiR-142-5p RAC1-PAK1 signaling |
| title | EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling |
| title_full | EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling |
| title_fullStr | EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling |
| title_full_unstemmed | EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling |
| title_short | EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling |
| title_sort | eif4a3 induced circbrwd3 promotes tumorigenesis of breast cancer through mir 142 3p mir 142 5p rac1 pak1 signaling |
| topic | Breast cancer EIF4A3 CircBRWD3 MiR-142-3p MiR-142-5p RAC1-PAK1 signaling |
| url | https://doi.org/10.1186/s12885-022-10200-7 |
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