Abstract
Purpose
Cisplatin 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.
Methods
The 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.
Results
In 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.
Conclusion
Our findings demonstrate that the lncRNA MIR4435-2HG is a main factor driving the cisplatin resistance of HCT116 cells.
Funder
the Natural Science Foundation of Jiangxi Province of China
Publisher
Public Library of Science (PLoS)
Reference21 articles.
1. Colon cancer, version 1.2017, NCCN clinical practice guidelines in oncology;AB Benson;J. Natl. Compr. Canc. Netw,2017
2. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial;A Grothey;Lancet,2013
3. Cisplatin resistance and opportunities for precision medicine;L Amable;Pharmacol. Res,2016
4. Systems biology of cisplatin resistance: past, present and future;L Galluzzi;Cell. Death. Dis,2014
5. Long noncoding RNAs: an emerging link between gene regulation and nuclear organization;S Quinodoz;Trends. Cell. Biol,2014
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