"非小细胞肺癌中的非编码 RNA 与转录因子 LRF 之间的相互影响

IF 5.9 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Magda Spella , Eleftherios Bochalis , Katerina Athanasopoulou , Argyri Chroni , Irene Dereki , Giannoula Ntaliarda , Ifigeneia Makariti , Georgios Psarias , Caterina Constantinou , Vasiliki Chondrou , Argyro Sgourou
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引用次数: 0

摘要

目前,与评估非小细胞肺癌(NSCLC)关键基因突变直接相关的表观遗传学方法非常密集,因为非小细胞肺癌发生和发展的表观遗传学因素已得到高度认可。在这一层次的研究中,已建立的人类 NSCLC 细胞系和实验动物被广泛用于检测治疗 NSCLC 的新型生物标记物和药物靶点。我们通过新一代测序(NGS)和实时定量 PCR(qPCR)深入分析了人 KRAS 突变 NSCLC 细胞系 A549 和 H460 以及小鼠 KRAS 突变 NSCLC 组织中普遍存在的非编码(nc)RNA。此外,还研究了转录因子(TF)LRF--一种已知的表观遗传沉默因子--对非编码 RNA 表达的调控作用。最后,我们创建了 NSCLC 亚型中表观遗传变异的相互作用网络。我们的研究数据强调了人类和小鼠来源的 NSCLC 表观遗传学特征的差异,以及 12qf1: 109,709,060-109,747,960 小鼠染色体区域对微 RNA 上调物种的重要贡献。此外,我们还发现了新的表观遗传 miR-148b-3p/lncPVT1/ZBTB7A 轴,它将人类肺腺癌细胞系与大细胞肺癌这两种特征性 NSCLC 亚型区分开来。对 NSCLC 中表观遗传事件的详细记录以及包括 ncRNA 和 TFs 之间网络的组合研究,验证了在 NSCLC 亚型和实验模型中普遍存在的重要表观遗传特征。我们的研究结果丰富了这一领域的知识,有助于研究疾病进展的表观遗传预后生物标志物、NSCLC 亚型鉴别以及推进针对患者的治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
“Crosstalk between non-coding RNAs and transcription factor LRF in non-small cell lung cancer”

Epigenetic approaches in direct correlation with assessment of critical genetic mutations in non-small cell lung cancer (NSCLC) are currently very intensive, as the epigenetic components underlying NSCLC development and progression have attained high recognition. In this level of research, established human NSCLC cell lines as well as experimental animals are widely used to detect novel biomarkers and pharmacological targets to treat NSCLC. The epigenetic background holds a great potential for the identification of epi-biomarkers for treatment response however, it is highly complex and requires precise definition as these phenomena are variable between NSCLC subtypes and systems origin.

We engaged an in-depth characterization of non-coding (nc)RNAs prevalent in human KRAS-mutant NSCLC cell lines A549 and H460 and mouse KRAS-mutant NSCLC tissue by Next Generation Sequencing (NGS) and quantitative Real Time PCRs (qPCRs). Also, the transcription factor (TF) LRF, a known epigenetic silencer, was examined as a modulator of non-coding RNAs expression. Finally, interacting networks underlying epigenetic variations in NSCLC subtypes were created. Data derived from our study highlights the divergent epigenetic profiles of NSCLC of human and mouse origin, as well as the significant contribution of 12qf1: 109,709,060–109,747,960 mouse chromosomal region to micro-RNA upregulated species. Furthermore, the novel epigenetic miR-148b-3p/lncPVT1/ZBTB7A axis was identified, which differentiates human cell line of lung adenocarcinoma from large cell lung carcinoma, two characteristic NSCLC subtypes.

The detailed recording of epigenetic events in NSCLC and combinational studies including networking between ncRNAs and TFs validate the identification of significant epigenetic features, prevailing in NSCLC subtypes and among experimental models. Our results enrich knowledge in the field and empower research on the epigenetic prognostic biomarkers of the disease progression, NSCLC subtypes discrimination and advancement to patient-tailored treatments.

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来源期刊
Non-coding RNA Research
Non-coding RNA Research Medicine-Biochemistry (medical)
CiteScore
7.70
自引率
6.00%
发文量
39
审稿时长
49 days
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.
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