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...

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Autores principales:	Jiang Xu, Zhongzu Zhang, Lu Huang, Jiachao Xiong, Zhenhai Zhou, Honggui Yu, Liang Wu, Zhimin Liu, Kai Cao
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Ewing sarcoma Cancer stem cells Let-7a STAT3 Lin28 Diseases of the musculoskeletal system RC925-935 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/86d85b06ad044546b9b2d8019234e2f8
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spelling	oai:doaj.org-article:86d85b06ad044546b9b2d8019234e2f82021-12-04T04:33:57ZLet-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin282212-137410.1016/j.jbo.2021.100406https://doaj.org/article/86d85b06ad044546b9b2d8019234e2f82021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2212137421000610https://doaj.org/toc/2212-1374Cancer 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.Jiang XuZhongzu ZhangLu HuangJiachao XiongZhenhai ZhouHonggui YuLiang WuZhimin LiuKai CaoElsevierarticleEwing sarcomaCancer stem cellsLet-7aSTAT3Lin28Diseases of the musculoskeletal systemRC925-935Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Bone Oncology, Vol 31, Iss , Pp 100406- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ewing sarcoma Cancer stem cells Let-7a STAT3 Lin28 Diseases of the musculoskeletal system RC925-935 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Ewing sarcoma Cancer stem cells Let-7a STAT3 Lin28 Diseases of the musculoskeletal system RC925-935 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
title	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_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_sort	let-7a suppresses ewing sarcoma cscs’ malignant phenotype via forming a positive feedback circuit with stat3 and lin28
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/86d85b06ad044546b9b2d8019234e2f8
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Let-7a suppresses Ewing sarcoma CSCs’ malignant phenotype via forming a positive feedback circuit with STAT3 and lin28

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