Knockdown Of IncRNA NCK-ASI Regulates Cisplatin Resistance Through Modulating miR-137 In Osteosarcoma Cells

Purpose: Long non-coding RNAs (IncRNAs) have been proved to act crucial parts in the progress of human tumor. However, the role of IncRNAs in drug resistance of tumor cells remains to be further elucidated. The present study aimed to explore whether IncRNA NCK-ASI could affect the cisplatin (DDP) re...

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Bibliographic Details
Published inOncoTargets and therapy p. 11057
Main Authors Cheng, Yi, Shen, Xiaofei, Zheng, Minqian, Zou, Guoyou, Shen, Yixin
Format Journal Article
LanguageEnglish
Published Dove Medical Press Limited 01.12.2019
Subjects
Cisplatin
Drug resistance
Genes
Genetic research
Luciferase
Novels
Osteosarcoma
RNA
Silence
Tumors
Wound care
Wound healing
Wounds
Japan
China
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Summary:Purpose: Long non-coding RNAs (IncRNAs) have been proved to act crucial parts in the progress of human tumor. However, the role of IncRNAs in drug resistance of tumor cells remains to be further elucidated. The present study aimed to explore whether IncRNA NCK-ASI could affect the cisplatin (DDP) resistance in human osteosarcoma cell and the underlying molecular mechanism. Methods: The expression of NCK1-AS1 and miR-137 in osteosarcoma cells was detected by qRT-PCR. CCK-8 assay, colony formation assay, Western blotting, wound healing assay and transwell assay were employed to assess the cell proliferation, migration and invasion. In addition, CCK-8 assay, flow cytometry, qRT-PCR and resistance gene activity analysis were performed to assess the DDP sensitivity of osteosarcoma cells. The interaction between NCK1-AS1 and miR-137 was identified using a dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. Results: The results revealed that NCK1-AS1 was significantly upregulated in osteosarcoma cells, as well as in DDP-resistant osteosarcoma cells. NCK1-AS1 silence inhibited the proliferation, migration and invasion of osteosarcoma cells, whereas enhanced the sensitivity of osteosarcoma cells to DDP. Furthermore, NCK1-AS1 directly interacted with miR-137 and overexpression of miR-137 suppressed the proliferation, migration and invasion of osteosarcoma cells. Most importantly, miR-137 overexpression enhanced the sensitivity of osteosarcoma cells to DDP, and high expression of NCK1-AS1 reversed the influences of miR-137 overexpression on DDP-resistant cells. Conclusion: In short, NCK1-AS1 knockdown enhanced DDP sensitivity of osteosarcoma cells by regulating miR-137, which may be a novel potential target for anti-DDP resistance in human osteosarcoma. Keywords: osteosarcoma, cisplatin, drug resistance, NCK1-AS1, miR-137
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S228199