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J Cell Mol Med ; 24(13): 7353-7369, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32558224

RESUMO

Emerging evidence has reported that dysregulation of microRNAs (miRNAs) participated in the development of diverse types of cancers. Our initial microarray-based analysis identified differentially expressed NEK2 related to breast cancer and predicted the regulatory microRNA-128-3p (miR-128-3p). Herein, this study aimed to characterize the tumour-suppressive role of miR-128-3p in regulating the biological characteristics of breast cancer stem cells (BCSCs). CD44+ CD24-/low cells were selected for subsequent experiments. After verification of the target relationship between miR-128-3p and NEK2, the relationship among miR-128-3p, NEK2 and BCSCs was further investigated with the involvement of the Wnt signalling pathway. The regulatory effects of miR-128-3p on proliferation, migration, invasion and self-renewal in vitro as well as tumorigenicity in vivo of BCSCs were examined via gain- and loss-of-function approaches. Highly expressed NEK2 was found in breast cancer based on GSE61304 expression profile. Breast cancer stem cells and breast cancer cells showed a down-regulation of miR-128-3p. Overexpression of miR-128-3p was found to inhibit proliferation, migration, invasion, self-renewal in vitro and tumorigenicity in vivo of BCSCs, which was further validated to be achieved through inhibition of Wnt signalling pathway by down-regulating NEK2. In summary, this study indicates that miR-128-3p inhibits the stem-like cell features of BCSCs via inhibition of the Wnt signalling pathway by down-regulating NEK2, which provides a new target for breast cancer treatment.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Quinases Relacionadas a NIMA/genética , Células-Tronco Neoplásicas/patologia , Via de Sinalização Wnt , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Autorrenovação Celular/genética , Feminino , Inativação Gênica , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Modelos Biológicos , Quinases Relacionadas a NIMA/metabolismo , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Regulação para Cima/genética
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