microRNA-21 Aggravates Lipopolysaccharide-Induced Inflammation in MH7A Cells Through Targeting SNF5.

The research aims to explore the roles and underlying mechanisms of microRNA-21 (miR-21) in lipopolysaccharide (LPS)-induced inflammation in MH7A cells. Cells were treated with LPS and/or transfected with miR-21 mimic/inhibitor or pc-sucrose nonfermentable 5 (SNF5). Cell viability was detected by CCK-8. ELISA and western blot were respectively conducted to measure the protein levels of pro-inflammatory factors, NF-κB or PTEN/PI3K/AKT key proteins and SNF5. miR-21/U6 was measured by qRT-PCR. The association between miR-21 and SNF5 was determined by luciferase reporter assay. Cell viability and the protein expression levels of interleukin-1ß (IL-1ß), IL-6, and p/t-p65, p/t-IκBα, p/t-PI3K, and p/t-AKT were significantly elevated by LPS, but with an inhibition of p-PTEN. Besides, LPS upregulated miR-21, whose overproduction or silence enhanced or alleviated the LPS stimulation on those elements above, respectively. miR-21 mimic notably inhibited SNF5, which was accelerated by miR-21 inhibitor, and abundant SNF5 abolished the effect of miR-21 mimic on cell viability, pro-inflammatory mediators, and sensitivity of signaling pathways, representing a negative relationship between them. miR-21 augmented LPS-induced inflammation response through activating NF-κB and PTEN/PI3K/AKT pathways by silencing SNF5 in MH7A cell line.

Preclinical Evaluation of Combined Targeted Approaches in Malignant Rhabdoid Tumors.

BACKGROUND/AIM: Rhabdoid tumors (RT) are aggressive pediatric tumors, which show poor prognosis despite use of multimodal intensive therapy. In these tumors, several different oncogenic pathways and epigenetic regulators (like CDK4/6-cyclinD-Rb-signaling, EZH2, histone deacetylases) are contemporaneously deregulated as a consequence of biallelic SMARCB1/SNF5/INI1 alterations. Since these tumors are highly resistant to current therapies, alternative treatment strategies are urgently required. MATERIALS AND METHODS: In this study, we evaluated cytotoxic effects (by MTT tests) of small molecular compounds, which specifically target these deregulated pathways, using either single-drug or combined approaches. Half-maximal inhibitory concentration (IC50) and combined index (CI) were calculated. RESULTS: All target-directed inhibitors blocked cell growth of three different rhabdoid tumor cell lines in vitro. Several combinations of those target-specific drugs synergistically inhibited cell proliferation of rhabdoid tumors. CONCLUSION: Supporting earlier reports, combined target-directed approaches are a promising tool for the therapy of malignant rhabdoid tumors.