Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer
Abstract Background miRNAs are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. miR-501-5p is newly identified to be involved in the tumor progression, but its biological role and mechanism remain largely unknown. This study is aimed to study the role...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2016-11-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-016-0432-x |
| _version_ | 1811303073707982848 |
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| author | Dongmei Fan Baoqi Ren Xiaojun Yang Jia Liu Zhengzheng Zhang |
| author_facet | Dongmei Fan Baoqi Ren Xiaojun Yang Jia Liu Zhengzheng Zhang |
| author_sort | Dongmei Fan |
| collection | DOAJ |
| description | Abstract Background miRNAs are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. miR-501-5p is newly identified to be involved in the tumor progression, but its biological role and mechanism remain largely unknown. This study is aimed to study the role of miR-501-5p in the progression of gastric cancer. Methods Real-time PCR analysis was used to determine miR-501-5p expression in gastric cancer cell lines, clinical tissues and 112 clinicopathologically characterized gastric cancer specimens. The role of miR-501-5p in maintaining gastric cancer stem cell like phenotype was examined by tumor-sphere formation assay and expression of stem cell markers. Luciferase reporter assay, cellular fractionation and western blot analysis were used to determined that miR-501-5p activated the wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β. Results Herein, our results revealed that miR-501-5p was markedly upregulated in gastric cancer cell lines and clinical tissues. High miR-501-5p levels predicted poor overall survival in gastric cancer patients. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-501-5p enhanced the cancer stem cell-like phenotype in gastric cancer cells. Notably,wnt/β-catenin signaling was hyperactivated in gastric cancer cells that overexpress miR-501-5p, and mediated miR-501-5p-induced cancer stem cell-like phenotype. Furthermore, miR-501-5p directly targeted and suppressed multiple repressors of the wnt/β-catenin signaling cascade, including DKK1, NKD1 and GSK3β. These results demonstrate that miR-501-5p maintains constitutively activated wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β, which promotes gastric cancer stem cell like phenotype. Conclusions Taken together, our findings reveal a new regulatory mechanism of miR-501-5p and suggest that miR-501-5p might be a potential target in gastric cancer therapy. |
| first_indexed | 2024-04-13T07:40:07Z |
| format | Article |
| id | doaj.art-5cd6ce6650ec4c548458a6cd8b6858f7 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T07:40:07Z |
| publishDate | 2016-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-5cd6ce6650ec4c548458a6cd8b6858f72022-12-22T02:55:55ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662016-11-013511910.1186/s13046-016-0432-xUpregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancerDongmei Fan0Baoqi Ren1Xiaojun Yang2Jia Liu3Zhengzheng Zhang4Department of Gastroenterology, First Affiliated Hospital of Guangzhou University of Chinese MedicineMedical Department of Guangdong Hospital of Traditional Chinese MedicineDepartment of Gastroenterology, First Affiliated Hospital of Guangzhou University of Chinese MedicineThird Affiliated Hospital of Guangzhou Medical CollegeDepartment of Gastroenterology, First Affiliated Hospital of Guangzhou University of Chinese MedicineAbstract Background miRNAs are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. miR-501-5p is newly identified to be involved in the tumor progression, but its biological role and mechanism remain largely unknown. This study is aimed to study the role of miR-501-5p in the progression of gastric cancer. Methods Real-time PCR analysis was used to determine miR-501-5p expression in gastric cancer cell lines, clinical tissues and 112 clinicopathologically characterized gastric cancer specimens. The role of miR-501-5p in maintaining gastric cancer stem cell like phenotype was examined by tumor-sphere formation assay and expression of stem cell markers. Luciferase reporter assay, cellular fractionation and western blot analysis were used to determined that miR-501-5p activated the wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β. Results Herein, our results revealed that miR-501-5p was markedly upregulated in gastric cancer cell lines and clinical tissues. High miR-501-5p levels predicted poor overall survival in gastric cancer patients. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-501-5p enhanced the cancer stem cell-like phenotype in gastric cancer cells. Notably,wnt/β-catenin signaling was hyperactivated in gastric cancer cells that overexpress miR-501-5p, and mediated miR-501-5p-induced cancer stem cell-like phenotype. Furthermore, miR-501-5p directly targeted and suppressed multiple repressors of the wnt/β-catenin signaling cascade, including DKK1, NKD1 and GSK3β. These results demonstrate that miR-501-5p maintains constitutively activated wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β, which promotes gastric cancer stem cell like phenotype. Conclusions Taken together, our findings reveal a new regulatory mechanism of miR-501-5p and suggest that miR-501-5p might be a potential target in gastric cancer therapy.http://link.springer.com/article/10.1186/s13046-016-0432-xmiR-501-5pGastric cancerWnt/β-catenin signalingCancer stem cell |
| spellingShingle | Dongmei Fan Baoqi Ren Xiaojun Yang Jia Liu Zhengzheng Zhang Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer Journal of Experimental & Clinical Cancer Research miR-501-5p Gastric cancer Wnt/β-catenin signaling Cancer stem cell |
| title | Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer |
| title_full | Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer |
| title_fullStr | Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer |
| title_full_unstemmed | Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer |
| title_short | Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer |
| title_sort | upregulation of mir 501 5p activates the wnt β catenin signaling pathway and enhances stem cell like phenotype in gastric cancer |
| topic | miR-501-5p Gastric cancer Wnt/β-catenin signaling Cancer stem cell |
| url | http://link.springer.com/article/10.1186/s13046-016-0432-x |
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