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OrthoDenticle Homeobox OTX1 是膀胱癌的一个潜在预后生物标志物。

Orthodenticle homeobox OTX1 is a potential prognostic biomarker for bladder cancer.

机构信息

Department of Emergency, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu City, China.

出版信息

Bioengineered. 2021 Dec;12(1):6559-6571. doi: 10.1080/21655979.2021.1974646.

Abstract

Bladder cancer (BC) is one of the most aggressive tumors worldwide. OTX1 (orthodenticle homeobox 1) is an important transcription factor involved in various diseases, such as cancers. The aim of this study was to further investigate the role of OTX1 in BC. In this study, differentially expressed genes (DEGs) were screened from tumor tissues and para-cancerous tissues by bioinformatics. The expression of protein and RNA was separately detected by western blotting and immunohistochemistry (IHC), and quantitative polymerase chain reaction (qPCR); cell viability and cell growth were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays, respectively; cell motility was measured by transwell and wound healing assays; cell cycle was measured by flow cytometry. In this study, 9 DEGs were screened out, and OTX1 was employed as a candidate gene for subsequent study. Results found that OTX1 was highly expressed in BC cells and BC tissues, which was significantly associated with poor prognosis of patients. In addition, OTX1 silencing significantly reduced cell viability, and inhibited cell growth and motility, while OTX1 overexpression got opposite results. Moreover, OTX1 co-expressed genes were enriched in cell cycle-related pathways, suggesting that the role of OTX1 in BC may be related to cell cycle, which was confirmed by flow cytometry analysis. Furthermore, experiments showed that OTX1 silencing significantly inhibited tumor growth in tumor-bearing mice. Taken together, our findings suggested that OTX1 may play a promotional role in BC progression.

摘要

膀胱癌(BC)是全球最具侵袭性的肿瘤之一。OTX1(orthodenticle homeobox 1)是一种重要的转录因子,涉及多种疾病,如癌症。本研究旨在进一步探讨 OTX1 在 BC 中的作用。本研究通过生物信息学从肿瘤组织和癌旁组织中筛选差异表达基因(DEGs)。分别通过蛋白质印迹法和免疫组织化学(IHC)和定量聚合酶链反应(qPCR)检测蛋白和 RNA 的表达;通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)和集落形成测定法分别测定细胞活力和细胞生长;通过 Transwell 和划痕愈合测定法分别测定细胞迁移;通过流式细胞术测定细胞周期。本研究筛选出 9 个 DEGs,其中 OTX1 作为候选基因进行后续研究。结果发现,OTX1 在 BC 细胞和 BC 组织中高表达,与患者的预后不良显著相关。此外,OTX1 沉默显著降低细胞活力,抑制细胞生长和迁移,而 OTX1 过表达则得到相反的结果。此外,OTX1 共表达基因富集在细胞周期相关途径中,表明 OTX1 在 BC 中的作用可能与细胞周期有关,这通过流式细胞术分析得到证实。进一步的实验表明,OTX1 沉默显著抑制荷瘤小鼠的肿瘤生长。综上所述,我们的研究结果表明,OTX1 可能在 BC 进展中发挥促进作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/025a/8806575/ecfc95e327c3/KBIE_A_1974646_F0001_OC.jpg

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