Wang Na, Qiao Hui, Hao Jianpeng, Deng Chenghui, Zhou Nan, Yang Lei, Zeng Miaomiao, Guan Quanlin
The First Clinical Medical College of Lanzhou University, Lanzhou, China.
Department of Oncology, Lanzhou University Second Hospital, Lanzhou, China.
J Gastrointest Oncol. 2023 Apr 29;14(2):585-598. doi: 10.21037/jgo-23-151. Epub 2023 Apr 17.
This study sought to identify the downstream target genes of enolase 1 (), clarify the role of in gastric cancer (GC), and provide novel insights into the regulatory mechanisms of in the occurrence and development of GC.
We performed RNA-immunoprecipitation sequencing in MKN-45 cells to study the types and abundance of pre-messenger RNA (mRNA)/mRNA bound by , the binding sites and motifs, the relationship between binding and its regulation of transcription level, and alternative splicing level by combining with RNA-sequencing (RNA-seq) data to further clarify the role of in GC.
We found that stabilized the expression of SRY-box transcription factor 9 (), vascular endothelial growth factor A (), G protein-coupled receptor class C group 5 member A (), and myeloid cell leukemia-1 () by binding to their mRNA, which increased the growth of GC. In addition, interacted with some other long non-coding RNAs (lncRNAs) or small-molecule kinases, such as , , , and pyruvate kinase M2 (), to regulate their expression to affect cell proliferation, migration, and apoptosis.
may play a role in GC by binding to and regulating GC-related genes. Our findings extend understandings of its mechanism as a clinical therapeutic target.
本研究旨在鉴定烯醇化酶1(ENO1)的下游靶基因,阐明ENO1在胃癌(GC)中的作用,并为ENO1在GC发生发展中的调控机制提供新见解。
我们在MKN-45细胞中进行了RNA免疫沉淀测序,以研究与ENO1结合的前体信使RNA(mRNA)/mRNA的类型和丰度、结合位点和基序、ENO1结合与其对转录水平的调控之间的关系,以及通过结合RNA测序(RNA-seq)数据来进一步阐明ENO1在GC中的作用。
我们发现ENO1通过与其mRNA结合来稳定SRY盒转录因子9(SOX9)、血管内皮生长因子A(VEGFA)、G蛋白偶联受体C类第5组成员A(GPRC5A)和髓样细胞白血病-1(MCL1)的表达,从而促进GC生长。此外,ENO1与一些其他长链非编码RNA(lncRNA)或小分子激酶相互作用,如HOTAIR、MALAT1、NEAT1和丙酮酸激酶M2(PKM2),以调节它们的表达来影响细胞增殖、迁移和凋亡。
ENO1可能通过结合并调控GC相关基因在GC中发挥作用。我们的发现扩展了对其作为临床治疗靶点机制的认识。