Let-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin28
Cancer stem cells (CSCs) have been documented to be closely related with tumor metastasis and recurrence, and the same important role were identified in Ewing Sarcoma (ES). In our previous study, we found that let-7a expression was repressed in ES. Herein, we further identified its putative effects...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Journal of Bone Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212137421000610 |
| _version_ | 1819097329812111360 |
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| author | Jiang Xu Zhongzu Zhang Lu Huang Jiachao Xiong Zhenhai Zhou Honggui Yu Liang Wu Zhimin Liu Kai Cao |
| author_facet | Jiang Xu Zhongzu Zhang Lu Huang Jiachao Xiong Zhenhai Zhou Honggui Yu Liang Wu Zhimin Liu Kai Cao |
| author_sort | Jiang Xu |
| collection | DOAJ |
| description | Cancer stem cells (CSCs) have been documented to be closely related with tumor metastasis and recurrence, and the same important role were identified in Ewing Sarcoma (ES). In our previous study, we found that let-7a expression was repressed in ES. Herein, we further identified its putative effects in the CSCs of ES (ES-CSCs). The expression of let-7a was consistently suppressed in the separated side population (SP) cells, which were identified to contain the characteristics of the stem cells. Then, we increased the expression of let-7a in ES-CSCs, and found that the ability of colony formation and invasion of ES-CSCs were suppressed in vitro. The same results were found in the tumor growth of ES-CSCs’ xenograft mice in vivo. To further explore the putative mechanism involved, we also explored whether signal transducer and activator of transcription 3 (STAT3) was involved in the suppressive effects. As expected, excessive expression of let-7a could suppress the expression STAT3 in the ES-CSCs, and repressed the expression of STAT3 imitated the suppressive effects of let-7a on ES-CSCs, suppressing the ability of colony formation and invasion of ES-CSCs. Furthermore, we found lin28 was involved in the relative impacts of let-7a, as well as STAT3. Let-7a, STAT3 and lin28 might form a positive feedback circuit, which serve a pivotal role in the carcinogensis of ES-CSCs. These findings maybe provide assistance for patients with ES in the future, especially those with metastasis and recurrence, and new directions for their treatment. |
| first_indexed | 2024-12-22T00:13:22Z |
| format | Article |
| id | doaj.art-86d85b06ad044546b9b2d8019234e2f8 |
| institution | Directory Open Access Journal |
| issn | 2212-1374 |
| language | English |
| last_indexed | 2024-12-22T00:13:22Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Bone Oncology |
| spelling | doaj.art-86d85b06ad044546b9b2d8019234e2f82022-12-21T18:45:22ZengElsevierJournal of Bone Oncology2212-13742021-12-0131100406Let-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin28Jiang Xu0Zhongzu Zhang1Lu Huang2Jiachao Xiong3Zhenhai Zhou4Honggui Yu5Liang Wu6Zhimin Liu7Kai Cao8Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR ChinaDepartment of Orthopedics, The Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, PR ChinaDepartment of Children Health and Care, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China; Corresponding author at: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China.Cancer stem cells (CSCs) have been documented to be closely related with tumor metastasis and recurrence, and the same important role were identified in Ewing Sarcoma (ES). In our previous study, we found that let-7a expression was repressed in ES. Herein, we further identified its putative effects in the CSCs of ES (ES-CSCs). The expression of let-7a was consistently suppressed in the separated side population (SP) cells, which were identified to contain the characteristics of the stem cells. Then, we increased the expression of let-7a in ES-CSCs, and found that the ability of colony formation and invasion of ES-CSCs were suppressed in vitro. The same results were found in the tumor growth of ES-CSCs’ xenograft mice in vivo. To further explore the putative mechanism involved, we also explored whether signal transducer and activator of transcription 3 (STAT3) was involved in the suppressive effects. As expected, excessive expression of let-7a could suppress the expression STAT3 in the ES-CSCs, and repressed the expression of STAT3 imitated the suppressive effects of let-7a on ES-CSCs, suppressing the ability of colony formation and invasion of ES-CSCs. Furthermore, we found lin28 was involved in the relative impacts of let-7a, as well as STAT3. Let-7a, STAT3 and lin28 might form a positive feedback circuit, which serve a pivotal role in the carcinogensis of ES-CSCs. These findings maybe provide assistance for patients with ES in the future, especially those with metastasis and recurrence, and new directions for their treatment.http://www.sciencedirect.com/science/article/pii/S2212137421000610Ewing sarcomaCancer stem cellsLet-7aSTAT3Lin28 |
| spellingShingle | Jiang Xu Zhongzu Zhang Lu Huang Jiachao Xiong Zhenhai Zhou Honggui Yu Liang Wu Zhimin Liu Kai Cao Let-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin28 Journal of Bone Oncology Ewing sarcoma Cancer stem cells Let-7a STAT3 Lin28 |
| title | Let-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin28 |
| title_full | Let-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin28 |
| title_fullStr | Let-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin28 |
| title_full_unstemmed | Let-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin28 |
| title_short | Let-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin28 |
| title_sort | let 7a suppresses ewing sarcoma cscs malignant phenotype via forming a positive feedback circuit with stat3 and lin28 |
| topic | Ewing sarcoma Cancer stem cells Let-7a STAT3 Lin28 |
| url | http://www.sciencedirect.com/science/article/pii/S2212137421000610 |
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