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长链非编码 RNA 通过调节 miR-138-5p/轴促进乳腺癌的进展。

Long Noncoding RNA Promotes the Progression of Breast Cancer by Regulating miR-138-5p/ Axis.

机构信息

Department of Medical Oncology Ward 2, The Third People's Hospital of Zhengzhou, Zhengzhou, China.

出版信息

Cancer Biother Radiopharm. 2022 Oct;37(8):636-649. doi: 10.1089/cbr.2019.3515. Epub 2020 Aug 21.

Abstract

Growing evidence demonstrated that long noncoding RNAs (lncRNAs) were involved in the progression of diverse cancers, including breast cancer (BC). Recent studies indicated that lncRNA nuclear enriched abundant transcript 1 () was overexpressed and facilitated tumor processes in many cancers. Nevertheless, the underlying mechanism of in regulating BC progression is still largely unknown. The abundance of , microRNA-138-5p (miR-138-5p), and zinc finger protein X-linked () was assessed by quantitative real-time polymerase chain reaction. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay were utilized to evaluate cell proliferation, apoptosis, migration, and invasion, respectively. Western blot analysis was applied to detect the protein expression of CyclinD1, Bax, E-cadherin, and . The interaction between miR-138-5p and or was predicted by starBase v3.0 and validated by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. The mice xenograft model was established to investigate the roles of . was highly expressed and miR-138-5p was lowly expressed in BC tissues and cells. interference or miR-138-5p restoration repressed cell proliferation, migration, and invasion but accelerated apoptosis in BC cells. Moreover, miR-138-5p directly interacted with and its knockdown reversed the suppressive impact of downregulation on the progression of BC cells. In addition, was a downstream target of miR-138-5p and its upregulation attenuated the antitumor role of miR-138-5p in BC cells. Besides, expression was positively regulated by and inversely modulated by miR-138-5p. Furthermore, interference of inhibited tumor growth by upregulating miR-138-5p and downregulating . affected BC progression through modulating miR-138-5p/ axis, providing a vital theoretical basis for BC treatment.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)参与了多种癌症的进展,包括乳腺癌(BC)。最近的研究表明,lncRNA 核富集丰富转录物 1()在许多癌症中过表达并促进肿瘤进程。然而,lncRNA 在调节 BC 进展中的潜在机制在很大程度上仍然未知。通过实时定量聚合酶链反应评估 abundance of 、microRNA-138-5p(miR-138-5p)和锌指蛋白 X 连锁()。细胞计数试剂盒-8(CCK-8) assay、流式细胞术和 Transwell assay 分别用于评估细胞增殖、凋亡、迁移和侵袭。Western blot analysis 用于检测 CyclinD1、Bax、E-cadherin 和 的蛋白表达。通过 starBase v3.0 预测 miR-138-5p 与 或 的相互作用,并通过双荧光素酶报告基因、RNA 下拉和 RNA 免疫沉淀assay 验证。建立小鼠异种移植模型以研究的作用。在 BC 组织和细胞中,表达上调,miR-138-5p 表达下调。干扰或 miR-138-5p 恢复抑制了 BC 细胞的增殖、迁移和侵袭,但加速了凋亡。此外,miR-138-5p 直接与相互作用,其下调逆转了下调对 BC 细胞进展的抑制作用。此外,是 miR-138-5p 的下游靶标,其上调减弱了 miR-138-5p 在 BC 细胞中的抗肿瘤作用。此外,表达受调节,miR-138-5p 上调和下调负调节表达。此外,通过上调 miR-138-5p 和下调,干扰抑制了肿瘤生长。通过调节 miR-138-5p/轴,影响 BC 的进展,为 BC 的治疗提供了重要的理论基础。

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