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- W3200980310 abstract "Multiple myeloma (MM) is a malignant cancer with an increasing in incidence that can be alleviated through bortezomib (BTZ) treatment. Activating transcription factor 3 (ATF3) plays a major role in cancer development. Moreover, microRNAs (miRNAs) regulate carcinogenic pathways, apoptosis, and programmed necrotic cell death. However, the detailed mechanism by which ATF3 modulates BTZ drug sensitivity/resistance remains elusive. In the current study, expression of ATF3 was significantly increased under BTZ treatment in a dose-dependent manner in MM cell lines. In addition, ATF3 could regulate cell apoptosis under BTZ treatment. The effect of ATF3 was negatively regulated by its binding miRNA, miR-135a-5p. When either ATF3 was silenced or miR-135a-5p mimics were added to MM cells, they partially lost sensitivity to BTZ treatment. This was accompanied by low levels of Noxa, CHOP, and DR5, and a decrease in mitochondrial membrane potential. These results revealed the combinatorial regulatory patterns of ATF3 and miR-135a-5p in the regulatory protein interactome, which indicated a clinical significance of the miR-135a-5p-ATF3 protein interaction network in BTZ therapy. This study provides potential evidence for further investigation into BTZ resistance." @default.
- W3200980310 created "2021-09-27" @default.
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- W3200980310 date "2021-09-22" @default.
- W3200980310 modified "2023-10-15" @default.
- W3200980310 title "Bortezomib Inhibits Multiple Myeloma Cells by Transactivating ATF3 to Trigger miR-135a-5p- Dependent Apoptosis" @default.
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- W3200980310 doi "https://doi.org/10.3389/fonc.2021.720261" @default.
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