{"title":"Circular RNA LMBR1 inhibits bladder cancer progression by enhancing expression of the protein ALDH1A3","authors":"Yifan Lv , Zusen Yuan , Dongmao Chen , Zhibin Chen , Xiaowei Zhu , Xiaoling Ying , Yapeng Huang , Weidong Ji , Defeng Qi","doi":"10.1016/j.ncrna.2024.05.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Circular RNAs (circRNAs) have been identified as playing an integral role in the development of bladder cancer (BC). However, the mechanism by which circRNAs operate in the chemical carcinogenesis of BC remains unclear.</p></div><div><h3>Methods</h3><p>To explore this mechanism, we used RNA high-throughput sequencing to identify differentially expressed circRNA in bladder epithelial cells and chemically induced malignant transformed BC cells. Subsequently, in <em>vitro</em> experiments were conducted to investigate the biological function and molecular mechanism of circLMBR1 in BC. Finally, animal experiments were conducted to examine the clinical relevance of circLMBR1 in <em>vivo</em>.</p></div><div><h3>Results</h3><p>Our profiling of circular RNA expression during cellular malignant transformation induced by chemical carcinogens identified a subset of circRNAs associated with cell transformation. We verified that the expression of circLMBR1 in bladder epithelial malignant transformed cells was decreased compared with control cells, as well as in BC tissues and bladder cell lines. Furthermore, circLMBR1 was seen to inhibit the proliferation, invasion, and migration of BC cells both in <em>vitro</em> and in <em>vivo</em>. Mechanistically, circLMBR1 was found to exert its antitumor effect by binding to the protein ALDH1A3.</p></div><div><h3>Conclusions</h3><p>Our findings have revealed that circLMBR1 inhibits the progression of BC cells by binding to ALDH1A3 and upregulating its expression. As such, circLMBR1 serves as a promising predictor of BC and may provide a novel therapeutic target for the treatment of BC.</p></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"9 4","pages":"Pages 1235-1248"},"PeriodicalIF":5.9000,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S246805402400091X/pdfft?md5=76bb19219879b9e39f2fce51253c0e45&pid=1-s2.0-S246805402400091X-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Non-coding RNA Research","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S246805402400091X","RegionNum":3,"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
Circular RNAs (circRNAs) have been identified as playing an integral role in the development of bladder cancer (BC). However, the mechanism by which circRNAs operate in the chemical carcinogenesis of BC remains unclear.
Methods
To explore this mechanism, we used RNA high-throughput sequencing to identify differentially expressed circRNA in bladder epithelial cells and chemically induced malignant transformed BC cells. Subsequently, in vitro experiments were conducted to investigate the biological function and molecular mechanism of circLMBR1 in BC. Finally, animal experiments were conducted to examine the clinical relevance of circLMBR1 in vivo.
Results
Our profiling of circular RNA expression during cellular malignant transformation induced by chemical carcinogens identified a subset of circRNAs associated with cell transformation. We verified that the expression of circLMBR1 in bladder epithelial malignant transformed cells was decreased compared with control cells, as well as in BC tissues and bladder cell lines. Furthermore, circLMBR1 was seen to inhibit the proliferation, invasion, and migration of BC cells both in vitro and in vivo. Mechanistically, circLMBR1 was found to exert its antitumor effect by binding to the protein ALDH1A3.
Conclusions
Our findings have revealed that circLMBR1 inhibits the progression of BC cells by binding to ALDH1A3 and upregulating its expression. As such, circLMBR1 serves as a promising predictor of BC and may provide a novel therapeutic target for the treatment of BC.
背景循环RNA(circRNA)已被确认在膀胱癌(BC)的发展中发挥着不可或缺的作用。为了探索这一机制,我们利用 RNA 高通量测序技术鉴定了膀胱上皮细胞和化学诱导的恶性转化 BC 细胞中表达不同的 circRNA。随后,我们通过体外实验研究了 circLMBR1 在 BC 中的生物学功能和分子机制。结果我们对化学致癌物质诱导的细胞恶性转化过程中循环 RNA 的表达进行了分析,发现了与细胞转化相关的循环 RNA 子集。我们证实,与对照细胞相比,circLMBR1 在膀胱上皮恶性转化细胞以及 BC 组织和膀胱细胞系中的表达均有所下降。此外,circLMBR1 在体外和体内均可抑制 BC 细胞的增殖、侵袭和迁移。结论我们的研究结果表明,circLMBR1 通过与 ALDH1A3 蛋白结合并上调其表达,抑制了 BC 细胞的进展。因此,circLMBR1 有望成为预测 BC 的指标,并为治疗 BC 提供新的治疗靶点。
期刊介绍:
Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.