Has_circ_0010220 regulates the miR-574-3p/IL-6 axis to increase doxorubicin resistance in osteosarcoma

下调和上调 骨肉瘤 阿霉素 基因沉默 癌症研究 抗药性 细胞生长 化学 分子生物学 化疗 医学 生物 内科学 基因 生物化学 微生物学
作者
Yanglin Gu,Guangchang Wang,Baocai Ran
出处
期刊:Human & Experimental Toxicology [SAGE]
卷期号:41 被引量:4
标识
DOI:10.1177/09603271221131307
摘要

Osteosarcoma (OS) is the most common primary bone malignancy. It has an aggressive nature and produces drug resistance in diseased patients, which in turn causes obstacles in treating cancer with chemotherapy. The objective of our investigation was to analyze the function and hsa_circ_0010220 mechanism in doxorubicin (DOX) resistance to OS.The hsa_circ_0010220, IL-6, and miR-574-3p levels in OS diseased tissues and cell resistance towards DOX drug were elucidated by qRT-PCR and Elisa assay. The DOX half-inhibitory concentration (IC50) was quantified by Cell Counting Kit-8. For this study, we used RNA pull-down, RNA immunoprecipitation, and a dual-luciferase reporter experiment to identify the proteins that interacted with has_circ_0010220, IL-6, and miR-574-3p in OS cells that have developed resistance towards DOX.The results indicated upregulated Hsa_circ_0010220 and IL-6 expression, However, DOX-resistant OS tissues and cells showed a downregulation of miR-574-3p. Reducing DOX resistance in vitro was achieved by silencing Has_circ_0010220. Further, by sponging miR-574-3p, increasing has_circ_0010220 boosted DOX resistance. However, miR-574-3p bound to IL-6 and inhibited DOX resistance. Additionally, it was discovered that hsa_circ_0010220 sponged miR-574-3p for upregulating IL-6 expression.Hsa_circ_0010220 encouraged OS resistance to DOX by miR-574-3p/IL-6 axis regulation, suggesting its potency as a promising biomarker for treating OS.

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