LncRNA NNT-AS1 contributes to the cisplatin resistance of cervical cancer through NNT-AS1/miR-186/HMGB1 axis

• Published in: Cancer cell international Vol. 20; no. 1; p. 190
• Main Authors: Liu, Yanjie, Guo, Ruixia, Qiao, Yuhuan, Han, Liping, Liu, Mingzhu
• Format: Journal Article
• Language: English
• Published: England BioMed Central 24.05.2020; BMC
• Subjects: Antisense RNA; Apoptosis; Bcl-2 protein; Bioinformatics; Cancer therapies; Caspase-3; Cell adhesion & migration; Cell migration; Cell proliferation; Cervical cancer; Cervix; Chemoresistance; Chemotherapy; Cisplatin; Cisplatin resistance; E-cadherin; Females; Flow cytometry; Gene expression; HMGB1; HMGB1 protein; Laboratory animals; Lung cancer; Manufacturers; Metastases; MicroRNAs; miR-186; miRNA; N-Cadherin; Nicotinamide; NNT-AS1; Polymerase chain reaction; Primary Research; Proteins; Vimentin; Xenografts; Beijing China; United States > US; China; NNT-AS1; Cisplatin resistance; HMGB1; miR-186; Cervical cancer
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-020-01278-9

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. 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. 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. NNT-AS1 improved chemoresistance of DDP-resistant CC cells via modulating miR-186/HMGB1 axis.