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MicroRNA 617 靶向丝氨酸蛋白酶抑制剂 1 抑制口腔鳞状细胞癌的进展。

MicroRNA 617 Targeting SERPINE1 Inhibited the Progression of Oral Squamous Cell Carcinoma.

机构信息

Department of Stomatology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, Hubei, China.

出版信息

Mol Cell Biol. 2021 May 21;41(6):e0056520. doi: 10.1128/MCB.00565-20.

Abstract

Serpin family E member 1 (SERPINE1) is a serine proteinase inhibitor (serpin) upregulated in diverse types of cancer, including oral squamous cell carcinoma (OSCC), and it functions in an oncogenic role. Hence, exploring pathological mechanism underlying high expression of SERPINE1 is crucial to the targeted therapy of OSCC. Bioinformatics analysis was performed to identify the microRNA (miRNA) and the candidate gene contributing to OSCC progression. The viability, proliferation, and apoptosis of the OSCC cell were evaluated using Cell Counting Kit-8 (CCK-8) assay, BrdU assay, and cell apoptosis assay, respectively. The RNA pulldown assay and luciferase reporter assay were conducted to verify the relationship between SERPINE1 and miRNA 617 (miR-617). SERPINE1 was aberrantly upregulated in OSCC tissues and cell lines. Genetically inhibiting SERPINE1 led to reduction of OSCC cell viability and proliferation and elevation of OSCC cell apoptosis. According to bioinformatics analysis, miR-617 contained a response element for SERPINE1 overexpression, which is validated by the RNA pulldown and luciferase reporter assays. Furthermore, miR-617 was detected to be downregulated in OSCC tissues and cell lines, and it displayed a negative correlation with advanced stages. Besides, miR-617 mimic or inhibitor transfection could suppress or boost the SERPINE1 expression. More importantly, miR-617 mimic could block the effect of SERPINE1 overexpression on OSCC cell proliferation, viability, and apoptosis. SERPINE1 acted as a proproliferative oncogenic factor that is partly regulated by miR-167 downregulation in OSCC cells. Therefore, the miR-617/SERPINE1 axis is a potential therapeutic target against OSCC.

摘要

丝氨酸蛋白酶抑制剂家族 E 成员 1(SERPINE1)是一种在多种癌症中上调的丝氨酸蛋白酶抑制剂(丝氨酸蛋白酶抑制剂),包括口腔鳞状细胞癌(OSCC),并发挥致癌作用。因此,探索 SERPINE1 高表达的病理机制对于 OSCC 的靶向治疗至关重要。进行了生物信息学分析,以确定有助于 OSCC 进展的 miRNA(miRNA)和候选基因。使用细胞计数试剂盒-8(CCK-8)测定、BrdU 测定和细胞凋亡测定分别评估 OSCC 细胞的活力、增殖和凋亡。进行 RNA 下拉测定和荧光素酶报告基因测定以验证 SERPINE1 和 miRNA 617(miR-617)之间的关系。SERPINE1 在 OSCC 组织和细胞系中异常上调。遗传抑制 SERPINE1 导致 OSCC 细胞活力和增殖减少,凋亡增加。根据生物信息学分析,miR-617 含有 SERPINE1 过表达的反应元件,该元件通过 RNA 下拉和荧光素酶报告基因测定得到验证。此外,miR-617 在 OSCC 组织和细胞系中检测到下调,并与晚期呈负相关。此外,miR-617 模拟物或抑制剂转染可抑制或增强 SERPINE1 的表达。更重要的是,miR-617 模拟物可阻断 SERPINE1 过表达对 OSCC 细胞增殖、活力和凋亡的影响。SERPINE1 作为一种促增殖的致癌因子,在 OSCC 细胞中部分受 miR-167 下调调节。因此,miR-617/SERPINE1 轴是针对 OSCC 的潜在治疗靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7fb/8316009/4f723153eef6/mcb.00565-20-f0001.jpg

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