Zhu Yu-Hui, Zhang Xin-Ru, Zhang Qi, Chai Jin
Department of Pharmacy, The Second Hospital of Jilin University, Changchun, China.
Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China.
Kaohsiung J Med Sci. 2022 May;38(5):447-456. doi: 10.1002/kjm2.12504. Epub 2022 Feb 17.
Icaritin has potential anticancer effects on various cancers, including multiple myeloma (MM). Recent studies claim that Icaritin can regulate the expression of noncoding RNAs (ncRNAs) in cancer development. This study aimed to investigate the role of circular RNA_0000190 (circ_0000190) and functional mechanism in Icaritin-treated MM. The expression of circ_0000190 and miR-301a was detected by quantitative real-time polymerase chain reaction. Cell cycle, apoptosis, migration, and invasion were investigated using flow cytometry assay, and transwell assay, respectively. The expression of BAX, BCL2, MMP2, and CCND1 was detected by western blot. The predicted target relationship between circ_0000190 and miR-301a was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. The activation of JAK1/STAT3 pathway was examined using western blot. Circ_0000190 was strikingly downregulated in MM specimens and cell lines, and Icaritin promoted the expression of circ_0000190. In function, circ_0000190 overexpression promoted MM cell cycle arrest and apoptosis but restrained the ability of migration and invasion. Icaritin blocked the development of MM by increasing circ_0000190 expression. MiR-301a was identified as a target of circ_0000190, and miR-301a reintroduction largely abolished the effects of circ_0000190 overexpression. The activation of JAK1/STAT3 pathway was promoted by miR-301a restoration. Icaritin played anticancer effects in MM partly by enhancing the expression of circ_0000190 and regulating the circ_0000190/miR-301a pathway. This study enhanced the understanding of the mechanism of Icaritin associated with circRNAs in MM.
淫羊藿素对包括多发性骨髓瘤（MM）在内的多种癌症具有潜在的抗癌作用。最近的研究表明，淫羊藿素在癌症发展过程中可调节非编码RNA（ncRNA）的表达。本研究旨在探讨环状RNA_0000190（circ_0000190）在淫羊藿素治疗MM中的作用及其功能机制。通过定量实时聚合酶链反应检测circ_0000190和miR-301a的表达。分别采用流式细胞术和Transwell实验研究细胞周期、凋亡、迁移和侵袭情况。通过蛋白质免疫印迹法检测BAX、BCL2、MMP2和CCND1的表达。通过双荧光素酶报告基因实验和RNA免疫沉淀实验验证circ_0000190与miR-301a之间的预测靶标关系。采用蛋白质免疫印迹法检测JAK1/STAT3通路的激活情况。在MM标本和细胞系中，circ_0000190显著下调，淫羊藿素可促进circ_0000190的表达。在功能上，circ_0000190过表达促进MM细胞周期停滞和凋亡，但抑制迁移和侵袭能力。淫羊藿素通过增加circ_0000190的表达来阻断MM的发展。miR-301a被确定为circ_0000190的靶标，重新导入miR-301a在很大程度上消除了circ_0000190过表达的影响。miR-301a的恢复促进了JAK1/STAT3通路的激活。淫羊藿素在MM中发挥抗癌作用部分是通过增强circ_0000190的表达并调节circ_0000190/miR-301a通路实现的。本研究加深了对淫羊藿素与circRNA在MM中相关机制的理解。
