MicroRNA-449a maintains self-renewal in liver cancer stem-like cells by targeting Tcf3
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Qianzhen Zhang1,2,*, Zhi Yang3,*, Juanjuan Shan3, Limei Liu3, Chungang Liu3, Junjie Shen3, Xuejiao Chen3, Yanmin Xu3, Jun Chen3, Qinghua Ma3, Li Yang1,2 and Cheng Qian3
1Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, China
2College of Bioengineering, Chongqing University, Chongqing, 400044, China
3Center of Biological Therapy, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
*These authors contributed equally to this work
Cheng Qian, email: [email protected]
Li Yang, email: [email protected]
Keywords: cancer stem cells; MicroRNA-449a; self-renewal; Nanog; TCF3
Received: October 07, 2017 Accepted: October 29, 2017 Published: November 27, 2017
Cancer stem cells (CSCs) are thought to be responsible for tumor invasion, metastasis, and recurrence. We previously showed that the pluripotency factor Nanog not only serves as a novel biomarker of CSCs but also potentially plays a crucial role in maintaining the self-renewal ability of liver CSCs. However, how CSCs maintain Nanog gene expression has not been elucidated. Here, we demonstrated that microRNA-449a (miR-449a) is overexpressed in poorly differentiated hepatocellular carcinoma tissues, drug-resistant liver cancer cells, cultured liver tumorspheres, and Nanog-positive liver cancer cells. The upregulation of miR-449a in non-CSCs increased stemness, whereas the downregulation of miR-449a in Nanog-positive CSCs reduced stemness. Furthermore, transcription factor 3 (TCF3), a target of miR-449a, could downregulate Nanog expression, and restoring TCF3 expression in miR-449a-expressing Nanog-negative cells abrogated cellular stemness. These data establish that the miR449a-TCF3-Nanog axis maintains stemness in liver CSCs.
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