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LncRNA NNT-AS1 contributes to the cisplatin resistance of cervical cancer through NNT-AS1/miR-186/HMGB1 axis
- Source :
- Cancer Cell International, Cancer Cell International, Vol 20, Iss 1, Pp 1-12 (2020)
- Publication Year :
- 2020
- Publisher :
- BioMed Central, 2020.
-
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.
- Subjects :
- Cancer Research
endocrine system diseases
lcsh:RC254-282
Flow cytometry
03 medical and health sciences
0302 clinical medicine
health services administration
Genetics
medicine
MTT assay
NNT-AS1
lcsh:QH573-671
Cisplatin resistance
030304 developmental biology
Cisplatin
HMGB1
0303 health sciences
Gene knockdown
medicine.diagnostic_test
Chemistry
Cell growth
lcsh:Cytology
Transfection
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
miR-186
Oncology
Apoptosis
Cell culture
030220 oncology & carcinogenesis
Cancer research
Cervical cancer
Primary Research
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 14752867
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Cancer Cell International
- Accession number :
- edsair.doi.dedup.....ca16fed98d194a2082997f70040e3efe