Hsa_circ_0000520 suppresses vasculogenic mimicry formation and metastasis in bladder cancer through Lin28a/PTEN/PI3K signaling.

IF 9.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cellular & Molecular Biology Letters Pub Date : 2024-09-05 DOI:10.1186/s11658-024-00627-0

Chunyu Zhang, Jiao Hu, Zhi Liu, Hao Deng, Jiatong Xiao, Zhenglin Yi, Yunbo He, Zicheng Xiao, Jinliang Huang, Haisu Liang, Benyi Fan, Zhihua Wang, Jinbo Chen, Xiongbing Zu

{"title":"Hsa_circ_0000520 suppresses vasculogenic mimicry formation and metastasis in bladder cancer through Lin28a/PTEN/PI3K signaling.","authors":"Chunyu Zhang, Jiao Hu, Zhi Liu, Hao Deng, Jiatong Xiao, Zhenglin Yi, Yunbo He, Zicheng Xiao, Jinliang Huang, Haisu Liang, Benyi Fan, Zhihua Wang, Jinbo Chen, Xiongbing Zu","doi":"10.1186/s11658-024-00627-0","DOIUrl":null,"url":null,"abstract":"Background: Vasculogenic mimicry (VM) is a potential cause of resistance to antiangiogenic therapy and is closely related to the malignant progression of tumors. It has been shown that noncoding RNAs play an important role in the formation of VM in malignant tumors. However, the role of circRNAs in VM of bladder cancer and the regulatory mechanisms are unclear.Methods: Firstly, hsa_circ_0000520 was identified to have circular character by Sanger sequencing and Rnase R assays. Secondly, the potential clinical value of hsa_circ_0000520 was explored by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) of clinical specimens. Thirdly, the role of hsa_circ_0000520 in bladder cancer invasion, migration, and VM formation was examined by in vivo and in vitro experiments. Finally, the regulatory mechanisms of hsa_circ_0000520 in the malignant progression of bladder cancer were elucidated by RNA binding protein immunoprecipitation (RIP), RNA pulldown, co-immunoprecipitation (co-IP), qRT-PCR, Western blot (WB), and fluorescence co-localization.Results: Hsa_circ_0000520 was characterized as a circular RNA and was lowly expressed in bladder cancer compared with the paracancer. Bladder cancer patients with high expression of hsa_circ_0000520 had better survival prognosis. Functionally, hsa_circ_0000520 inhibited bladder cancer invasion, migration, and VM formation. Mechanistically, hsa_circ_0000520 acted as a scaffold to promote binding of UBE2V1/UBC13 to Lin28a, further promoting the ubiquitous degradation of Lin28a, improving PTEN mRNA stability, and inhibiting the phosphorylation of the PI3K/AKT pathway. The formation of hsa_circ_0000520 in bladder cancer was regulated by RNA binding protein QKI.Conclusions: Hsa_circ_0000520 inhibits metastasis and VM formation in bladder cancer and is a potential target for bladder cancer diagnosis and treatment.","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"118"},"PeriodicalIF":9.2000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378395/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular & Molecular Biology Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s11658-024-00627-0","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Vasculogenic mimicry (VM) is a potential cause of resistance to antiangiogenic therapy and is closely related to the malignant progression of tumors. It has been shown that noncoding RNAs play an important role in the formation of VM in malignant tumors. However, the role of circRNAs in VM of bladder cancer and the regulatory mechanisms are unclear.

Methods: Firstly, hsa_circ_0000520 was identified to have circular character by Sanger sequencing and Rnase R assays. Secondly, the potential clinical value of hsa_circ_0000520 was explored by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) of clinical specimens. Thirdly, the role of hsa_circ_0000520 in bladder cancer invasion, migration, and VM formation was examined by in vivo and in vitro experiments. Finally, the regulatory mechanisms of hsa_circ_0000520 in the malignant progression of bladder cancer were elucidated by RNA binding protein immunoprecipitation (RIP), RNA pulldown, co-immunoprecipitation (co-IP), qRT-PCR, Western blot (WB), and fluorescence co-localization.

Results: Hsa_circ_0000520 was characterized as a circular RNA and was lowly expressed in bladder cancer compared with the paracancer. Bladder cancer patients with high expression of hsa_circ_0000520 had better survival prognosis. Functionally, hsa_circ_0000520 inhibited bladder cancer invasion, migration, and VM formation. Mechanistically, hsa_circ_0000520 acted as a scaffold to promote binding of UBE2V1/UBC13 to Lin28a, further promoting the ubiquitous degradation of Lin28a, improving PTEN mRNA stability, and inhibiting the phosphorylation of the PI3K/AKT pathway. The formation of hsa_circ_0000520 in bladder cancer was regulated by RNA binding protein QKI.

Conclusions: Hsa_circ_0000520 inhibits metastasis and VM formation in bladder cancer and is a potential target for bladder cancer diagnosis and treatment.

查看原文本刊更多论文

Hsa_circ_0000520通过Lin28a/PTEN/PI3K信号传导抑制膀胱癌血管生成模拟的形成和转移。

背景：血管生成模拟（VM）是抗血管生成治疗耐药的潜在原因，与肿瘤的恶性进展密切相关。研究表明，非编码 RNA 在恶性肿瘤 VM 的形成过程中发挥着重要作用。然而，circRNAs在膀胱癌VM中的作用及其调控机制尚不清楚：方法：首先，通过桑格测序和 Rnase R 检测确定 hsa_circ_0000520 具有环状特征。第二，通过对临床标本进行实时定量聚合酶链反应（qRT-PCR）和荧光原位杂交（FISH），探讨了 hsa_circ_0000520 的潜在临床价值。第三，通过体内和体外实验研究了hsa_circ_0000520在膀胱癌侵袭、迁移和血管瘤形成中的作用。最后，通过RNA结合蛋白免疫沉淀（RIP）、RNA pulldown、共免疫沉淀（co-IP）、qRT-PCR、Western blot（WB）和荧光共定位等方法阐明了hsa_circ_0000520在膀胱癌恶性进展过程中的调控机制：结果：Hsa_circ_0000520是一种环状RNA，在膀胱癌中的表达量低于癌旁RNA。高表达 hsa_circ_0000520 的膀胱癌患者生存预后较好。在功能上，hsa_circ_0000520能抑制膀胱癌的侵袭、迁移和血管瘤的形成。从机理上讲，hsa_circ_0000520可作为支架促进UBE2V1/UBC13与Lin28a结合，进一步促进Lin28a的泛在降解，提高PTEN mRNA的稳定性，抑制PI3K/AKT通路的磷酸化。Hsa_circ_0000520在膀胱癌中的形成受RNA结合蛋白QKI的调控：结论：Hsa_circ_0000520能抑制膀胱癌的转移和血管瘤的形成，是膀胱癌诊断和治疗的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cellular & Molecular Biology Letters 生物-生化与分子生物学

CiteScore

11.60

自引率

13.30%

发文量

101

审稿时长

3 months

期刊介绍： Cellular & Molecular Biology Letters is an international journal dedicated to the dissemination of fundamental knowledge in all areas of cellular and molecular biology, cancer cell biology, and certain aspects of biochemistry, biophysics and biotechnology.