miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling
A number of studies have reported that aberrant expression of microRNAs (miRNAs) closely correlates with the bone metastasis of prostate cancer (PCa). However, clinical significance and functional roles of both strands of a single miRNA in bone metastasis of PCa remain undefined. Here, we reported t...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119300071 |
| _version_ | 1818301462396010496 |
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| author | Shuai Huang Changye Zou Yubo Tang Qingde Wa Xinsheng Peng Xiao Chen Chunxiao Yang Dong Ren Yan Huang Zhuangwen Liao Sheng Huang Xuenong Zou Jincheng Pan |
| author_facet | Shuai Huang Changye Zou Yubo Tang Qingde Wa Xinsheng Peng Xiao Chen Chunxiao Yang Dong Ren Yan Huang Zhuangwen Liao Sheng Huang Xuenong Zou Jincheng Pan |
| author_sort | Shuai Huang |
| collection | DOAJ |
| description | A number of studies have reported that aberrant expression of microRNAs (miRNAs) closely correlates with the bone metastasis of prostate cancer (PCa). However, clinical significance and functional roles of both strands of a single miRNA in bone metastasis of PCa remain undefined. Here, we reported that miR-582-3p and miR-582-5p expression were simultaneously reduced in bone metastatic PCa tissues compared with non-bone metastatic PCa tissues. Downexpression of miR-582-3p and miR-582-5p strongly and positively correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients. Upregulating miR-582-3p and miR-582-5p inhibited invasion and migration abilities of PCa cells in vitro, as well as repressed bone metastasis in vivo. Our results further revealed that miR-582-3p and miR-582-5p attenuated bone metastasis of PCa via inhibiting transforming growth factor β (TGF-β) signaling by simultaneously targeting several components of TGF-β signaling, including SMAD2, SMAD4, TGF-β receptor I (TGFBRI), and TGFBRII. Moreover, deletion contributes to miR-582-3p and miR-582-5p downexpression in PCa tissues. Finally, clinical negative correlations of miR-582-3p and miR-582-5p with SMAD2, SMAD4, TGFBRI, and TGFBRII were demonstrated in PCa tissues. Thus, our findings explore a novel tumor-suppressive miRNA with its both strands implicated in bone metastasis of PCa, suggesting its potential therapeutic value in treatment of PCa bone metastasis. |
| first_indexed | 2024-12-13T05:23:24Z |
| format | Article |
| id | doaj.art-9220508953394330a828aa42892b7ccf |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-13T05:23:24Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-9220508953394330a828aa42892b7ccf2022-12-21T23:58:15ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-06-011691104miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β SignalingShuai Huang0Changye Zou1Yubo Tang2Qingde Wa3Xinsheng Peng4Xiao Chen5Chunxiao Yang6Dong Ren7Yan Huang8Zhuangwen Liao9Sheng Huang10Xuenong Zou11Jincheng Pan12Department of Orthopaedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, 510260 Guangzhou, China; Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, China; Corresponding author: Shuai Huang, Department of Orthopaedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, 510620 Guangzhou, China.Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, ChinaDepartment of Orthopaedic Surgery, The Affiliated Hospital of Zunyi Medical College, 563003 Zunyi, ChinaDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, ChinaDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, ChinaDepartment of Orthopaedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, 510260 Guangzhou, ChinaDepartment of Orthopaedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, 510260 Guangzhou, ChinaDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Nanchang University, 330006 Nanchang, ChinaDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, China; Corresponding author: Xuenong Zou, Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, 510080 Guangzhou, China.Department of Urology Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Corresponding author: Jincheng Pan, Department of Urology Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, 510080 Guangzhou, China.A number of studies have reported that aberrant expression of microRNAs (miRNAs) closely correlates with the bone metastasis of prostate cancer (PCa). However, clinical significance and functional roles of both strands of a single miRNA in bone metastasis of PCa remain undefined. Here, we reported that miR-582-3p and miR-582-5p expression were simultaneously reduced in bone metastatic PCa tissues compared with non-bone metastatic PCa tissues. Downexpression of miR-582-3p and miR-582-5p strongly and positively correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients. Upregulating miR-582-3p and miR-582-5p inhibited invasion and migration abilities of PCa cells in vitro, as well as repressed bone metastasis in vivo. Our results further revealed that miR-582-3p and miR-582-5p attenuated bone metastasis of PCa via inhibiting transforming growth factor β (TGF-β) signaling by simultaneously targeting several components of TGF-β signaling, including SMAD2, SMAD4, TGF-β receptor I (TGFBRI), and TGFBRII. Moreover, deletion contributes to miR-582-3p and miR-582-5p downexpression in PCa tissues. Finally, clinical negative correlations of miR-582-3p and miR-582-5p with SMAD2, SMAD4, TGFBRI, and TGFBRII were demonstrated in PCa tissues. Thus, our findings explore a novel tumor-suppressive miRNA with its both strands implicated in bone metastasis of PCa, suggesting its potential therapeutic value in treatment of PCa bone metastasis.http://www.sciencedirect.com/science/article/pii/S2162253119300071 |
| spellingShingle | Shuai Huang Changye Zou Yubo Tang Qingde Wa Xinsheng Peng Xiao Chen Chunxiao Yang Dong Ren Yan Huang Zhuangwen Liao Sheng Huang Xuenong Zou Jincheng Pan miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling Molecular Therapy: Nucleic Acids |
| title | miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling |
| title_full | miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling |
| title_fullStr | miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling |
| title_full_unstemmed | miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling |
| title_short | miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling |
| title_sort | mir 582 3p and mir 582 5p suppress prostate cancer metastasis to bone by repressing tgf β signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119300071 |
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