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环状 RNA 的微阵列表达谱分析及其在膀胱癌中的潜在调控作用。

Microarray expression profile analysis of circular RNAs and their potential regulatory role in bladder carcinoma.

机构信息

Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China.

出版信息

Oncol Rep. 2021 Jan;45(1):239-253. doi: 10.3892/or.2020.7849. Epub 2020 Nov 12.

Abstract

Dysregulated circular RNAs (circRNAs) often contribute to the occurrence and development of various tumors; however, the function and mechanism of circRNAs are largely unknown in human bladder cancer (BC). In the present study, dysregulated circRNAs between BC and adjacent non‑neoplastic bladder tissues were analyzed by circRNA microarray. We randomly selected 10 upregulated and five downregulated circRNAs for validation by quantitative real‑time PCR. Bioinformatics analysis was further conducted to investigate the potential function of these differentially expressed circRNAs, with the differential expression of hsa_circRNA_100876, mir‑136‑5p, and mRNA‑chromobox 4 (CBX4) subsequently verified. A total of 512 differentially expressed circRNAs were identified after scanning and normalization (340 upregulated and 172 downregulated circRNAs), with pathway and Gene Ontology analyses revealing their association with multiple significant cancer pathways. Construction of a circRNA‑microRNA‑mRNA network suggested additional potential roles of these circRNAs. The expression of hsa_circRNA_100876 and CBX4 was significantly negatively correlated with the expression of miR‑136‑5p. Additionally, hsa_circRNA_100876 was highly positively correlated with CBX4 expression. The results revealed that hsa_circRNA_100876 inhibition suppressed BC cell proliferation and it was associated with advanced T stage and lymphatic metastasis, and poor overall survival of BC patients. In conclusion, these differentially expressed circRNAs offer novel insights into potential biological markers or new therapeutic targets for the treatment of BC. Furthermore, hsa_circRNA_100876 may increase the expression of CBX4 by competing with miR‑136‑5p, ultimately promoting the malignant biological behavior of BC. Aberrantly expressed hsa_circRNA_100876 could be used as a potential non‑invasive biomarker for the early detection and screening of BC.

摘要

失调的环状 RNA(circRNAs)通常有助于各种肿瘤的发生和发展;然而,环状 RNA 在人类膀胱癌(BC)中的功能和机制在很大程度上尚不清楚。在本研究中,通过环状 RNA 微阵列分析了 BC 和相邻非肿瘤性膀胱组织之间失调的环状 RNA。我们随机选择了 10 个上调和 5 个下调的环状 RNA 进行定量实时 PCR 验证。进一步进行生物信息学分析,以研究这些差异表达的环状 RNA 的潜在功能,随后验证了 hsa_circRNA_100876、mir-136-5p 和 mRNA-盒蛋白 4(CBX4)的差异表达。扫描和归一化后鉴定出 512 个差异表达的 circRNA(340 个上调和 172 个下调 circRNA),通路和基因本体分析显示它们与多种重要的癌症途径有关。构建 circRNA-miRNA-mRNA 网络表明这些 circRNA 具有额外的潜在作用。hsa_circRNA_100876 和 CBX4 的表达与 miR-136-5p 的表达呈显著负相关。此外,hsa_circRNA_100876 与 CBX4 的表达高度正相关。结果表明,hsa_circRNA_100876 抑制抑制 BC 细胞增殖,并与 T 期晚期和淋巴转移有关,BC 患者的总生存率较差。总之,这些差异表达的 circRNA 为潜在的生物标志物或治疗 BC 的新治疗靶点提供了新的见解。此外,hsa_circRNA_100876 可能通过与 miR-136-5p 竞争来增加 CBX4 的表达,最终促进 BC 的恶性生物学行为。异常表达的 hsa_circRNA_100876 可作为 BC 早期检测和筛查的潜在非侵入性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e26c/7716712/089a3952084e/OR-45-01-0239-g00.jpg

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