环状RNA在非小细胞肺癌中的作用:鉴定靶点和新的治疗方式。

IF 2.6 4区 医学 Q2 GENETICS & HEREDITY Cancer Genomics & Proteomics Pub Date : 2023-12-01 DOI:10.21873/cgp.20413
Ulrich H Weidle, Fabian Birzele
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引用次数: 0

摘要

尽管非小细胞肺癌(NSCLC)有多种治疗选择,如手术、化疗、放疗、靶向治疗和免疫治疗,但患者的5年生存率在22%左右。因此,确定这种疾病的新靶点和治疗方式是一个重要问题。在此背景下,我们在PubMed数据库中筛选了在体外临床前模型和免疫受损小鼠体内异种移植模型中促进非小细胞肺癌生长的上调环状rna (circRNAs)。这种方法为进一步验证和抑制小分子或抗体衍生实体提供了潜在的靶点。在临床前验证的情况下,可以用小干扰rna (siRNA)或短发夹rna (shRNA)抑制相应的环状rna。鉴定的环状rna通过海绵状的microrna (miRs)阻止相应靶标mRNA的切割。我们发现9个circRNAs上调跨膜受体,5个circRNAs增加分泌蛋白的表达,9个circRNAs促进信号通路组分的表达,6个circRNAs参与剪接和RNA加工的调节,6个circRNAs上调动作蛋白相关和RNA加工组分,7个circRNAs增加转录因子的稳态水平,2个circRNAs增加高迁移率组蛋白。四种环状rna增加表观遗传修饰系统的成分,三种环状rna上调其他系统的蛋白质成分。
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Circular RNA in Non-small Cell Lung Carcinoma: Identification of Targets and New Treatment Modalities.

Despite availability of several treatment options for non-small cell lung cancer (NSCLC), such as surgery, chemotherapy, radiation, targeted therapy and immunotherapy, the survival rate of patients for five years is in the range of 22%. Therefore, identification of new targets and treatment modalities for this disease is an important issue. In this context, we screened the PubMed database for up-regulated circular RNAs (circRNAs) which promote growth of NSCLC in preclinical models in vitro as well as in vivo xenograft models in immuno-compromised mice. This approach led to potential targets for further validation and inhibition with small molecules or antibody-derived entities. In case of preclinical validation, the corresponding circRNAs can be inhibited with small interfering RNAs (siRNA) or short hairpin RNAs (shRNA). The identified circRNAs act by sponging microRNAs (miRs) preventing cleavage of the mRNA of the corresponding targets. We identified nine circRNAs up-regulating transmembrane receptors, five circRNAs increasing expression of secreted proteins, nine circRNAs promoting expression of components of signaling pathways, six circRNAs involved in regulation of splicing and RNA processing, six circRNAs up-regulating actin-related and RNA processing components, seven circRNAs increasing the steady-state levels of transcription factors, two circRNAs increasing high-mobility group proteins, four circRNAs increasing components of the epigenetic modification system and three circRNAs up-regulating protein components of additional systems.

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来源期刊
Cancer Genomics & Proteomics
Cancer Genomics & Proteomics ONCOLOGY-GENETICS & HEREDITY
CiteScore
5.00
自引率
8.00%
发文量
51
期刊介绍: Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004. Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal. Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.
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