Downregulation of lncRNA H19 sensitizes melanoma cells to cisplatin by regulating the miR-18b/IGF1 axis.
ANTI-CANCER DRUGS(2020)
Abstract
Long noncoding RNAs (LncRNAs) lncRNA H19 has been shown to be involved in the chemotherapy resistance of cancer cells. However, the role of lncRNA H19 in chemotherapy resistance of melanoma cells remains unknown. Here, we determined lncRNA H19, miR-18b, and insulin-like growth factor 1 (IGF1) expression by utilizing quantitative real-time PCR. Cell proliferation ability and chemosensitivity were assessed by colony formation assay and MTT assay. Flow cytometry assay was applied to detect cell apoptosis. We discovered that lncRNA H19 was upregulated, but miR-18b was downregulated in melanoma tissues and cisplatin (DDP)-resistant melanoma cells. The overall survival for the group with lower lncRNA H19 was significantly better than the group with higher H19. IGF1 mRNA level was higher in melanoma tissues than that in normal tissues. miR-18b expression level A negative correlation was observed between the expression levels of miR-18b, lncRNA H19, and IGF1 mRNA. Functionally, knockdown of lncRNA H19 sensitized resistant A375/DDP and M8/DDP cells to DDP. Silencing lncRNA H19 inhibited colony formation ability and promoted apoptosis of DDP-resistant melanoma cells, which was abrogated by miR-18b inhibition and IGF1 upregulation. Mechanistically, lncRNA H19 directly interacted with miR-18b to regulate its expression. IGF1 was identified as a target of miR-18b. These findings highlight the fact that lncRNA H19 could influence DDP-resistance by modulating the miR-18b/IGF axis in melanoma cells, suggesting a new potential therapeutic target for melanoma patient treatment.
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Key words
cisplatin,insulin-like growth factor 1,long noncoding RNA H19,melanoma,miR-18b
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