RESUMO
An increasing body of evidence suggests that long noncoding RNAs play critical roles in human cancer. Breast cancer is a heterogeneous disease and the potential involvement of long noncoding RNAs in breast cancer remains poorly understood. Herein, the study identified a long noncoding RNA, DANCR, which promotes cisplatin chemoresistance in triple-negative breast cancer (TNBC) cells. Mechanistically, binding of DANCR to Krüppel-like factor 5 (KLF5) induced acetylation of KLF5 at lysine 369 (K369), and DANCR knockdown resulted in down-regulation of KLF5 protein levels. Furthermore, DANCR/KLF5 signaling pathway induced hypersensitivity to cisplatin in chemoresistant patients by inhibiting p27 transcription. In summary, this study reinforced the potential presence of a growth regulatory network in TNBC cells, and documented a DANCR/KLF5/p27 signaling pathway mediating cisplatin chemoresistance in TNBC.
Assuntos
RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , Cisplatino/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição/metabolismo , Transdução de Sinais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão GênicaRESUMO
Inadequate endometrial receptivity is a key factor affecting the successful implantation of embryos. Recombinant human granulocyte colony stimulating factor (rhG-CSF) can increase endometrial thickness and improve the outcomes of assisted reproductive technologies (ARTs). In this preliminary study, the function and possible molecular mechanisms of recombinant human granulocyte colony stimulating factor (rhG-CSF) which affects endometrial receptivity and implantation in human Embryonic Stem Cells (hESCs) were investigated. The cell viability of endometrial stromal cells treated with rhG-CSF 0.5 ng/ml for 24 h was significantly increased. Moreover, the expression of hsa_circ_0001550 was downregulated in endometrial stromal cells treated with rhG-CSF. Furthermore, the hsa_circ_0001550-miRNA-mRNA network was constructed and the downstream target genes (including 4 miRNAs and 117 mRNAs) of hsa_circ_0001550 were mainly involved in the cAMP and calcium signalling pathways, which play important roles in regulating endometrial receptivity and embryo implantation. We conclude that rhG-CSF participates in the regulation of embryo implantation by regulating the hsa_circ_0001550-miRNA-mRNA interaction network.
