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Multiple myeloma is the second most common hematological malignancy. Trifluoperazine (TFP), an antipsychotic drug, has been reported to exert antitumor effects. Here, our results indicate that TFP targets NUPR1, inhibiting cell growth and inducing apoptosis by autophagy inhibition in multiple myeloma cells. This study provides more directions for the treatment for multiple myeloma.

Multiple myeloma (MM) is a heterogeneous disease with poor prognosis. Increasing evidence has revealed that microRNAs (miRNAs) are strongly associated with the pathogenesis and progression of MM. Here, we investigated the role of microRNA-637 (miR-637) in MM to identify potential therapeutic targets. We measured the expression of miR-637 in bone marrow samples of MM patients and MM cell lines by quantitative real-time PCR and western blot. The effect of miR-637 on proliferation and apoptosis of MM primary cells was also investigated. Analyses of four bioinformatics databases showed that miR-637 is associated with nuclear protein 1 (NUPR1) in MM cells, which was confirmed by luciferase reporter assay. We found that the overexpression of miR-637 suppressed the development of MM. miR-637 mimics increased the levels of Bax, cleaved caspase 3, and P62, and decreased the levels of Bcl2 and LC3. Additionally, luciferase reporter assays were performed to demonstrate that NUPR1 is the main target of miR-637 in MM cells. Overexpression of NUPR1 reversed the effects of miR-637 mimics in MM cells. Our results suggest that miR-637 inhibits cell proliferation and autophagy, and promotes apoptosis in MM cells by targeting NUPR1. Our findings also suggest that miR-637 may have potential as a novel molecular therapeutic target for MM treatment.

Background Nonalcoholic steatohepatitis (NASH) is one of the most frequent liver diseases at present, and there is no radical treatment. The consequences of a variety of ginsenoside compounds on this situation have before been reported, however, the specific effect on the monomeric ginsenoside Rg1 (Rg1) and its associated underlying molecular mechanism stay unknown. Material and methods In vitro, the cell models were constructed by exposing free fatty acids (FFAs) to HepG2 cells. A methionine and choline deficiency (MCD)-induced NASH mouse model was also established over 5–6 weeks of treatment. Rg1 is a traditional Chinese medicine monomer. These NASH models were treated with Rg1 and analyzed by qRT-PCR, Western Blot, sequencing, Oil red O staining, immunofluorescence, enzyme activity, HE staining, ELISA, double luciferase reporter assay, and immunohistochemistry. Results Overexpression of ATG2B, an autophagy-related protein, attenuated lipid droplet accumulation and reduces ALT, AST, inflammatory cytokines, hydrogen peroxide, and pyroptosis in established mouse and cellular models of NASH and increased levels of ATP and autophagy. The binding sites of miR-375-3p and ATG2B were verified by bioinformatic prediction and a dual-luciferase reporter gene. Knockdown of miR-375-3p promoted autophagy and inhibited pyroptosis. ATG2B knockdown substantially attenuated the impact of miR-375-3p on NASH. Rg1 appears to regulate the occurrence and development of NASH inflammation through miR-375-3p and ATG2B in vitro and in vivo, and is regulated by PTEN-AKT pathway. Conclusions This study showed that Rg1 participates in autophagy and pyroptosis through the miR-375-3p/ATG2B/PTEN-AKT pathway, thereby alleviating the occurrence and development of NASH, for that reason revealing Rg1 as a candidate drug for NASH.

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