MiR-34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene.
作者： Youguang Pu , Fangfang Zhao , Haiyan Wang , Shanbao Cai
DOI: 10.1038/SREP44218
关键词: Regulation of gene expression 、 Osteosarcoma 、 Signal transduction 、 Cancer research 、 Notch signaling pathway 、 Carcinogenesis 、 microRNA 、 Programmed cell death 、 Apoptosis 、 Biology
摘要: MiR-34a-5p has been implicated in the tumorigenesis and progression of several types cancer. However, role miR-34a-5p osteosarcoma (OS) remains largely unknown. This study was performed two multi-chemosensitive (G-292 MG63.2) resistant (SJSA-1 MNNG/HOS) OS cell lines. promotes multi-chemoresistance via its repression Delta-like ligand 1 (DLL1) gene, Notch pathway, thus negatively correlates with chemoresistance. The siRNA-mediated DLL1 gene suppressed apoptosis de-sensitized G-292 MG63.2 cells, while overexpression sensitized SJSA-1 MNNG/HOS cells to drug-induced death. In agreement changes death, activity ATF2/ATF3/ATF4 signaling pathway significantly altered by a forced reversal or levels cells. is target regulates OS. suggested that miR-34a-5p, pathway-associated genes are potential diagnostic and/or therapeutic targets for an effective chemotherapy Our results also provide novel insights into patients.
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