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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Liu, Yanjie Guo, Ruixia Qiao, Yuhuan Han, Liping Liu, Mingzhu |
| Abstract | Background Cisplatin (DDP) is a major chemotherapeutic drug which was widely used for cervical cancer (CC) patients with advanced or recurrent although its limitation in the development of resistance. LncRNA nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) has been reported to be involved in the DDP resistance. However, the role of NNT-AS1 in DDP resistance in CC remain unknown. Methods The mRNA expression of NNT-AS1, microRNA-186 (miR-186) and HMGB1 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and apoptosis abilities were measured via MTT assay or flow cytometry, respectively. Western blot was used to measure the expression level of HMGB1, Bax, Bcl-2, Cleaved-caspase 3, N-cadherin, Vimentin and E-cadherin. Cell migration and invasion abilities were analyzed using Transwell assay. The interaction among NNT-AS1, miR-186 and HMGB1 was confirmed by luciferase reporter assay and RNA pull-down assay. Murine xenograft model was established using stably transfected SiHa/DDP cells. Results NNT-AS1 level was significantly elevated in CC tissues and cells, especially in DDP-resistant tumors and cell lines. Subsequently, loss-of function assays indicated that NNT-AS1 silence could attenuate DDP resistance by inhibiting proliferation, metastasis and EMT but inducing apoptosis in DDP-resistant CC cells. Besides that, knockdown of NNT-AS1 also antagonized DDP resistance in vivo. Bioinformatics predication revealed NNT-AS1 directly bound to miR-186 and HMGB1 was a target of miR-186. Additionally, NNT-AS1 could regulate HMGB1 expression via targeting miR-186. Furthermore, restoration experiments showed NNT-AS1 knockdown might improve DDP-sensitivity of CC cells via blocking HMGB1 expression by competitive interaction with miR-186. Conclusion NNT-AS1 improved chemoresistance of DDP-resistant CC cells via modulating miR-186/HMGB1 axis. |
| Related Links | https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-020-01278-9.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14752867 |
| DOI | 10.1186/s12935-020-01278-9 |
| Journal | Cancer Cell International |
| Issue Number | 1 |
| Volume Number | 20 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2020-05-24 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Cell Biology NNT-AS1 miR-186 HMGB1 Cisplatin resistance Cervical cancer |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Genetics Oncology |
| Journal Impact Factor | 5.3/2023 |
| 5-Year Journal Impact Factor | 5/2023 |
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