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Cancers 2019, 11(4), 518;

Identification of Cancer Stem Cell Molecular Markers and Effects of hsa-miR-21-3p on Stemness in Esophageal Squamous Cell Carcinoma

1,†, 2,†, 1, 1, 3 and 1,*
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210000, China
Chengdu Center for Disease Control and Prevention, Chengdu 610000, China
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06510, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 11 March 2019 / Revised: 1 April 2019 / Accepted: 8 April 2019 / Published: 11 April 2019
(This article belongs to the Special Issue Advances in Cancer Stem Cell Research)
PDF [46691 KB, uploaded 11 April 2019]


Cancer stem cells (CSCs) are closely related to tumor resistance and tumor recurrence in esophageal squamous cell carcinoma (ESCC). The lack of specific biomarkers to identify and isolate CSCs has led to the slow progression of research on CSCs in ESCC. Here, we established a method to identify and isolate CSCs in ESCC using fluorescence-activated cell sorting with combined surface biomarkers including CD71, CD271, and CD338. CD71/CD271+/CD338+ subpopulation cells possessed more stem cell properties in proliferation, self-renewal, differentiation, metastasis, drug resistance, and tumorigenesis. We further explored possible roles that microRNAs played in stem cells. Using microarrays, we identified that has-miR-21-3p was highly expressed in positive sorted cells, and further functional and Luciferase reporter assays verified that has-miR-21-3p promoted proliferation and anti-apoptosis by regulating TRAF4. We further analyzed the relationship between hsa-miR-21-3p and ESCC in 137 patients with ESCC. Statistical analysis showed that up-regulation of hsa-miR-21-3p was associated with a high risk of ESCC. Collectively, we identified surface biomarkers of stem cells in esophageal squamous cell carcinoma, and discovered thathsa-miR-21-3p may be involved in stemness maintenance by regulating TRAF4. View Full-Text
Keywords: esophageal squamous cell carcinoma; cancer stem cell; Hsa-miR-21-3p; TRAF4 esophageal squamous cell carcinoma; cancer stem cell; Hsa-miR-21-3p; TRAF4

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Gao, Z.; Liu, H.; Shi, Y.; Yin, L.; Zhu, Y.; Liu, R. Identification of Cancer Stem Cell Molecular Markers and Effects of hsa-miR-21-3p on Stemness in Esophageal Squamous Cell Carcinoma. Cancers 2019, 11, 518.

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