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长链非编码RNA SENP3-EIF4A1作为miR-195-5p的海绵,通过过度表达CCNE1来驱动三阴性乳腺癌进展。

Long Non-coding RNA SENP3-EIF4A1 Functions as a Sponge of miR-195-5p to Drive Triple-Negative Breast Cancer Progress by Overexpressing CCNE1.

作者信息

Chen Lie, Miao Xiaofei, Si Chenchen, Qin An, Zhang Ye, Chu Chunqiang, Li Zengyao, Wang Tong, Liu Xiao

机构信息

Department of Thyroid and Breast Surgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.

Department of General Surgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.

出版信息

Front Cell Dev Biol. 2021 Mar 15;9:647527. doi: 10.3389/fcell.2021.647527. eCollection 2021.

Abstract

Triple-negative breast cancer (TNBC) has high malignancy and limited treatment, so novel molecular therapeutic targets are urgently needed. Cyclin E1 (CCNE1) promotes progression in breast cancer, but its role and inherent mechanisms in TNBC are yet to be elucidated. Competing endogenous RNA (ceRNA) may be a potential mechanism. CCNE1 was selected though bioinformatics and clinical samples, and cell lines were utilized to verify CCNE1 expression by qRT-PCR and western blot. Predicting tools provided potential miR-195-5p and SENP3-EIF4A1 and tested from multilevel. Functional experiments were conducted and . Luciferase reporter assay and RNA immunoprecipitation experiments were implemented to ensure the interaction between miR-195-5p and SENP3-EIF4A1/CCNE1 in TNBC. Bioinformatics found DNA hypermethylation of miR-195-5p and preliminarily verified. Mechanistically, SENP3-EIF4A1-miR-195-5p-associated ceRNA could drive TNBC progress though regulating CCNE1. DNA hypermethylation of miR-195-5p might be another reason. In summary, SENP3-EIF4A1-miR-195-5p-CCNE1 axis promotes TNBC progress and may contribute to the novel diagnosis and treatment of TNBC.

摘要

三阴性乳腺癌(TNBC)具有高恶性和有限的治疗手段,因此迫切需要新的分子治疗靶点。细胞周期蛋白E1(CCNE1)促进乳腺癌进展,但其在TNBC中的作用及内在机制尚待阐明。竞争性内源RNA(ceRNA)可能是一种潜在机制。通过生物信息学和临床样本筛选出CCNE1,并利用细胞系通过qRT-PCR和蛋白质免疫印迹法验证CCNE1表达。预测工具提供了潜在的miR-195-5p和SENP3-EIF4A1,并进行了多层次测试。进行了功能实验。实施荧光素酶报告基因检测和RNA免疫沉淀实验以确定miR-195-5p与TNBC中SENP3-EIF4A1/CCNE1之间的相互作用。生物信息学发现miR-195-5p的DNA高甲基化并进行了初步验证。机制上,SENP3-EIF4A1-miR-195-5p相关的ceRNA可能通过调节CCNE1推动TNBC进展。miR-195-5p的DNA高甲基化可能是另一个原因。总之,SENP3-EIF4A1-miR-195-5p-CCNE1轴促进TNBC进展,可能有助于TNBC的新诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c7/8006396/edbbdb476b6e/fcell-09-647527-g0001.jpg

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