Lncrna Mir4435-2hg Mediates Cisplatin Resistance In Hct116 Cells By Regulating Nrf2 And Ho-1

PLOS ONE(2020)

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Abstract
PurposeCisplatin resistance is still a serious problem in the clinic. However, the underlying mechanism remains unknown. In our study, we investigated cisplatin resistance by using the cisplatin-resistant cell line HCT116R.MethodsThe HCT116 cell line, a colon cancer cell line, was purchased. Cell viability was determined using CCK-8 Assay Kit. The gene expression levels of MIR4435-2HG, Nrf2, and HO-1, and caspase activity were determined using qRT-PCR and Caspase 3 Assay Kit, respectively.ResultsIn this study, we found that the levels of the lncRNA MIR4435-2HG were dramatically increased in the cisplatin-resistant cell line HCT116R. Knockdown of MIR4435-2HG in HCT116R cells significantly restored the sensitivity to cisplatin, inhibited cell proliferation and promoted cell apoptosis. Furthermore, Nrf2 and HO-1 mRNA levels, as critical molecules in the oxidative stress pathway, were inhibited by siRNAs targeting MIR4435-2HG, suggesting that MIR4435-2HG-mediated cisplatin resistance occurs through the Nrf2/HO-1 pathway.ConclusionOur findings demonstrate that the lncRNA MIR4435-2HG is a main factor driving the cisplatin resistance of HCT116 cells.
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