Downregulation of circular RNA hsa_circ_0087856 sensitizes bladder cancer cells to cisplatin through targeting miR-1184/CITED2 signaling

IF 2.3 4区 医学 Q3 ENVIRONMENTAL SCIENCES Environmental and Molecular Mutagenesis Pub Date : 2023-07-01 DOI:10.1002/em.22561
Min Ju, Weiwei Wu, Jingkun Qu, Yang Sun, Jun Li
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Abstract

CircRNAs are considered as one of the potential therapeutic targets of multiple cancers. According to accumulating evidence, circRNA regulates cancer progression by acting as a miRNA sponge. In the current work, our data discovered that hsa_circ_0087856 and CITED2 expression was increased, while miR-1184 expression was decreased in BC cell lines and tissues. Hsa_circ_0087856 expression negatively correlated with miR-1184, whereas positively correlated with CITED2. Hsa_circ_0087856 silencing suppressed BC tumor growth, and contributed to the inhibition of cisplatin to tumor growth. In cellular experiments, hsa_circ_0087856 increasing promoted BC cells proliferation, migration and invasion, and inhibited the cells apoptosis. Hsa_circ_0087856 increasing partly reversed the inhibition of cisplatin to BC cell proliferation and the promotion to cell apoptosis. Oppositely, hsa_circ_0087856 silencing could increase the sensitivity of BC cells to cisplatin. Hsa_circ_0087856 promoted CITED2 expression through binding with miR-1184 and inhibiting its expression. CITED2 increasing partly reversed the promotion of hsa_circ_0087856 silencing to cisplatin-induced BC cells apoptosis promotion and proliferation suppression. Overall, our results revealed the role of hsa_circ_0087856 that downregulation its expression could enhance the BC cells sensitivity to cisplatin by facilitating CITED expression via sponging miR-1184. Moreover, our research provided a potential therapeutic target for BC.

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下调环状RNA hsa_circ_0087856通过靶向miR-1184/CITED2信号通路使膀胱癌细胞对顺铂敏感
环状rna被认为是多种癌症的潜在治疗靶点之一。根据越来越多的证据,circRNA通过充当miRNA海绵来调节癌症的进展。在目前的工作中,我们的数据发现hsa_circ_0087856和CITED2在BC细胞系和组织中表达升高,而miR-1184表达降低。Hsa_circ_0087856表达与miR-1184呈负相关,与CITED2呈正相关。Hsa_circ_0087856沉默抑制BC肿瘤生长,并有助于顺铂抑制肿瘤生长。在细胞实验中,hsa_circ_0087856的增加促进了BC细胞的增殖、迁移和侵袭,抑制了细胞的凋亡。Hsa_circ_0087856的升高部分逆转了顺铂抑制BC细胞增殖和促进细胞凋亡的作用。相反,hsa_circ_0087856沉默可增加BC细胞对顺铂的敏感性。Hsa_circ_0087856通过与miR-1184结合并抑制其表达来促进CITED2的表达。CITED2的增加部分逆转了hsa_circ_0087856沉默对顺铂诱导的BC细胞凋亡促进和增殖抑制的促进作用。总之,我们的研究结果揭示了hsa_circ_0087856的作用,下调其表达可以通过海绵化miR-1184促进引用表达来增强BC细胞对顺铂的敏感性。此外,我们的研究为BC提供了一个潜在的治疗靶点。
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来源期刊
CiteScore
5.40
自引率
10.70%
发文量
52
审稿时长
12-24 weeks
期刊介绍: Environmental and Molecular Mutagenesis publishes original research manuscripts, reviews and commentaries on topics related to six general areas, with an emphasis on subject matter most suited for the readership of EMM as outlined below. The journal is intended for investigators in fields such as molecular biology, biochemistry, microbiology, genetics and epigenetics, genomics and epigenomics, cancer research, neurobiology, heritable mutation, radiation biology, toxicology, and molecular & environmental epidemiology.
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