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β-细辛醚通过UCA1/miR-206/NRP1轴抑制视网膜母细胞瘤细胞中的卡铂耐药性。

β-Asarone Inhibits Carboplatin Resistance in Retinoblastoma Cells Through the UCA1/miR-206/NRP1 Axis.

作者信息

Bai Shuwei, Wang Haiyan, Bai Ye, Liu Peiyang, Bi Chunchao

机构信息

Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, No. 21 Jiefang Rd, Xi'an, 710004, Shaanxi, China.

出版信息

Biochem Genet. 2024 Dec 24. doi: 10.1007/s10528-024-10985-1.

DOI:10.1007/s10528-024-10985-1
PMID:39718722
Abstract

Retinoblastoma (RB) is an aggressive form of eye cancer. β-Asarone is a bioactive component isolated from the medicinal plant Acorus tatarinowii Schott and has anticancer effects on various human cancers. However, reports regarding the role of β-Asarone in RB remain limited. Our study investigates the mechanisms of β-Asarone in regulating drug resistance in RB, providing a theoretical foundation for RB treatment. A carboplatin-resistant RB cell line was established and treated with β-Asarone, followed by overexpression of long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1). The half-maximal inhibitory concentration and cell apoptosis were determined. The levels of lncRNA UCA1/miR-206/neuropilin 1 (NRP1) were measured. The subcellular localization of lncRNA UCA1 was examined. The binding relationships between lncRNA UCA1 and microRNA (miR)-206, and between miR-206 and NRP1 were analyzed. NRP1 expression was analyzed by Western blot assay. We found that β-Asarone downregulated lncRNA UCA1 expression in carboplatin-resistant RB cells. Overexpression of lncRNA UCA1 reversed the inhibitory effect of β-Asarone on cell drug resistance and cell proliferation and reduced apoptosis. LncRNA UCA1 functioned as a sponge for miR-206, which suppressed NRP1 expression. Inhibition of miR-206 or overexpression of NRP1 could partially reverse the suppressive effect of β-Asarone on RB cell drug resistance. In conclusion, β-Asarone suppresses RB cell drug resistance through the lncRNA UCA1/miR-206/NRP1 axis.

摘要

视网膜母细胞瘤(RB)是一种侵袭性眼癌。β-细辛醚是从药用植物石菖蒲中分离出的一种生物活性成分,对多种人类癌症具有抗癌作用。然而,关于β-细辛醚在RB中的作用的报道仍然有限。我们的研究探讨了β-细辛醚调节RB耐药性的机制,为RB治疗提供理论基础。建立了耐卡铂的RB细胞系并用β-细辛醚处理,随后过表达长链非编码RNA(lncRNA)尿路上皮癌相关1(UCA1)。测定了半数最大抑制浓度和细胞凋亡情况。检测了lncRNA UCA1/miR-206/神经纤毛蛋白1(NRP1)的水平。检查了lncRNA UCA1的亚细胞定位。分析了lncRNA UCA1与微小RNA(miR)-206之间以及miR-206与NRP1之间的结合关系。通过蛋白质免疫印迹法分析NRP1表达。我们发现β-细辛醚下调了耐卡铂RB细胞中lncRNA UCA1的表达。lncRNA UCA1的过表达逆转了β-细辛醚对细胞耐药性和细胞增殖的抑制作用,并减少了细胞凋亡。lncRNA UCA1作为miR-206的海绵发挥作用,miR-206抑制NRP1表达。抑制miR-206或过表达NRP1可部分逆转β-细辛醚对RB细胞耐药性的抑制作用。总之,β-细辛醚通过lncRNA UCA1/miR-206/NRP1轴抑制RB细胞耐药性。

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The Neuropilin-1/PKC axis promotes neuroendocrine differentiation and drug resistance of prostate cancer.神经纤毛蛋白-1/蛋白激酶 C 轴促进前列腺癌的神经内分泌分化和耐药性。
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