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微小 RNA-218-5p 通过靶向内质网氧化还原酶 1α 影响肺腺癌的进展。

MicroRNA-218-5p affects lung adenocarcinoma progression through targeting endoplasmic reticulum oxidoreductase 1 alpha.

机构信息

Internal Medicine-oncology, The First People's Hospital Of Jiashan, Jiaxing, China.

Department of Clinical Medicine, The Second Hospital of Dalian Medical University, Dalian, China.

出版信息

Bioengineered. 2022 Apr;13(4):10061-10070. doi: 10.1080/21655979.2022.2063537.

Abstract

Lung adenocarcinoma (LUAD) severely threatens the health of people owing to its lethality. Nonetheless, the underlying mechanisms on LUAD development remain unclear to a great extent. This work aimed to probe the functions of miR-218-5p in LUAD. MiR-218-5p and endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) were screened as differently downregulated and upregulated RNAs in LUAD, respectively, by bioinformatics analyses. The results of cell functional assays stated that enforced expression of miR-218-5p notably restrained cell viability, invasion, and migration in LUAD. MiR-218-5p may interact with 3'-untranslated region of ERO1A mRNA as analyzed by bioinformatics. Afterward, western blot and dual-luciferase reporter gene analyses were introduced to identify their interaction. ERO1A overexpression reversed the suppressive impacts of miR-218-5p on LUAD cell progression, indicating the implication of miR-218-5p/ERO1A axis in suppressing cancer development. We also observed that this regulatory axis suppressed angiogenesis in LUAD. Taken together, miR-218-5p/ERO1A axis exerted an imperative role in LUAD cell progression, which provides a valuable clue for the development of LUAD therapeutic regimen.

摘要

肺腺癌(LUAD)因其致命性严重威胁着人们的健康。然而,LUAD 发展的潜在机制在很大程度上仍不清楚。本研究旨在探讨 miR-218-5p 在 LUAD 中的功能。通过生物信息学分析,分别筛选出 miR-218-5p 和内质网氧化还原酶 1α(ERO1A)分别是 LUAD 中下调和上调的 RNA。细胞功能测定结果表明,miR-218-5p 的强制表达显著抑制 LUAD 细胞的活力、侵袭和迁移。通过生物信息学分析,miR-218-5p 可能与 ERO1A mRNA 的 3'-非翻译区相互作用。随后,进行了 Western blot 和双荧光素酶报告基因分析以鉴定其相互作用。ERO1A 的过表达逆转了 miR-218-5p 对 LUAD 细胞进展的抑制作用,表明 miR-218-5p/ERO1A 轴在抑制癌症发展中的作用。我们还观察到该调节轴抑制了 LUAD 中的血管生成。总之,miR-218-5p/ERO1A 轴在 LUAD 细胞进展中发挥着重要作用,为 LUAD 治疗方案的制定提供了有价值的线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f638/9161986/724da70fa77a/KBIE_A_2063537_UF0001_OC.jpg

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