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LINC00467 通过 miR-299-5p/泛素特异性蛋白酶-48 轴促进头颈部鳞状细胞癌的进展和上皮-间充质转化过程。

LINC00467 enhances head and neck squamous cell carcinoma progression and the epithelial-mesenchymal transition process via miR-299-5p/ubiquitin specific protease-48 axis.

机构信息

Department of Stomatology, The Affiliated Hanyang Hospital of Wuhan University of Science and Technology, Wuhan, China.

Department of Outpatient Service, the Affiliated Hanyang Hospital of Wuhan University of Science and Technology, Wuhan, China.

出版信息

J Gene Med. 2020 Jul;22(7):e3184. doi: 10.1002/jgm.3184. Epub 2020 Apr 18.

Abstract

BACKGROUND

Head and neck squamous cell carcinoma (HNSCC) has attracted the attention of researchers as a result of its high incidence around the world. This malignancy occurs in the oral cavity, pharynx and larynx in most cases. A number of lncRNAs have been revealed to regulate the malignant neoplasia of several cancers. Nevertheless, the effects of lncRNA LINC00467 in HNSCC have not yet been reported.

METHODS

The expression of LINC00467, miR-299-5p and ubiquitin specific protease-48 (USP48) in HNSCC cells was quantified by a quantitative reverse transcriptase-polymerase chain reaction. The influences of LINC00467 deficiency on HNSCC progression were reflected by cell counting kit-8, colony formation, ethynyl-2-deoxyuridine, wound healing and western blot assays. RIP and luciferase reporter assays were conducted to confirm the interaction among LINC00467, miR-299-5p and USP48.

RESULTS

LINC00467 was considerably upregulated in HNSCC cells, and an absence of LINC00467 suppressed cell growth, cell migration and the epithelial-mesenchymal process in HNSCC. In addition, miR-299-5p expression was notably downregulated in HNSCC cells, and miR-299-5p could bind with LINC00467. Furthermore, USP48 was conspicuously overexpressed in HNSCC cells and capable of binding with miR-299-5p. LINC00467 could upregulate USP48 expression via sponging miR-299-5p. Finally, rescue assays proved that USP48 overexpression could compensate for the suppressive effects on HNSCC progression mediated by LINC00467 deficiency.

CONCLUSIONS

LINC00467 enhances HNSCC progression by serving as a sponge of miR-299-5p to increase USP48 expression.

摘要

背景

头颈部鳞状细胞癌(HNSCC)由于其在全球的高发病率而引起了研究人员的关注。这种恶性肿瘤在大多数情况下发生在口腔、咽和喉。已经发现许多长链非编码 RNA 可以调节几种癌症的恶性肿瘤。然而,lncRNA LINC00467 在 HNSCC 中的作用尚未报道。

方法

通过定量逆转录聚合酶链反应定量检测 HNSCC 细胞中 LINC00467、miR-299-5p 和泛素特异性蛋白酶 48(USP48)的表达。通过细胞计数试剂盒-8、集落形成、乙炔-2-脱氧尿苷、伤口愈合和 Western blot 分析来反映 LINC00467 缺乏对 HNSCC 进展的影响。RIP 和荧光素酶报告基因检测用于证实 LINC00467、miR-299-5p 和 USP48 之间的相互作用。

结果

LINC00467 在 HNSCC 细胞中显著上调,缺乏 LINC00467 可抑制 HNSCC 细胞的生长、迁移和上皮-间充质转化。此外,miR-299-5p 在 HNSCC 细胞中的表达显著下调,miR-299-5p 可以与 LINC00467 结合。此外,USP48 在 HNSCC 细胞中显著过表达,并且能够与 miR-299-5p 结合。LINC00467 可以通过海绵 miR-299-5p 上调 USP48 的表达。最后,挽救实验证明,USP48 的过表达可以补偿 LINC00467 缺乏对 HNSCC 进展的抑制作用。

结论

LINC00467 通过作为 miR-299-5p 的海绵来增加 USP48 的表达,从而增强 HNSCC 的进展。

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