Knock-down of microRNA miR-556-5p increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via activating NLR family pyrin domain containing 3 (NLRP3)-mediated pyroptotic cell death.
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| Abstract |
MicroRNAs (miRNAs) are small non-coding RNAs that are closely associated with cancer progression and drug resistance, however, up until now, the involvement of miR-556-5p in regulating cisplatin-sensitivity in non-small cell lung cancer (NSCLC) has not been studied. In the present study, we found that miR-556-5p was significantly upregulated in the cisplatin-resistant NSCLC (CR-NSCLC) patients' tissues and cells, instead of the corresponding cisplatin-sensitive NSCLC (CS-NSCLC) tissues and cells. Further experiments validated that knock-down of miR-556-5p suppressed cell viability and tumorigenesis, and induced cell apoptosis in the cisplatin-treated CR-NSCLC cells, and conversely, upregulation of miR-556-5p increased cisplatin-resistance in CS-NSCLC cells. Interestingly, miR-556-5p ablation triggered pyroptotic cell death in cisplatin-treated CR-NSCLC cells via upregulating NLRP3, and the promoting effects of miR-556-5p silence on cisplatin-sensitivity in CR-NSCLC cells were abrogated by both cell pyroptosis inhibitor NSA and NLRP3 downregulation. Taken together, this study firstly evidenced that induction of NLRP3-mediated cell pyroptosis by miR-556-5p downregulation was effective to increase cisplatin-sensitivity in NSCLC, which provided new therapy strategies to overcome chemo-resistance for NSCLC patients in clinic.
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| Authors | Feng Shi, Luquan Zhang, Xing Liu, Yue Wang |
| Journal | Bioengineered (Bioengineered) Vol. 12 Issue 1 Pg. 6332-6342 (12 2021) ISSN: 2165-5987 [Electronic] United States |
| PMID | 34488537 (Publication Type: Journal Article) |
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