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.

中文翻译：

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MicroRNA 617 靶向 SERPINE1 抑制口腔鳞状细胞癌的进展

Serpin 家族 E 成员 1 (SERPINE1) 是一种丝氨酸蛋白酶抑制剂 (serpin)，在包括口腔鳞状细胞癌 (OSCC) 在内的多种癌症中上调，并且具有致癌作用。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。进行生物信息学分析以鉴定微小RNA (miRNA)和有助于OSCC进展的候选基因。分别使用细胞计数试剂盒-8 (CCK-8) 测定、BrdU 测定和细胞凋亡测定评估 OSCC 细胞的活力、增殖和凋亡。进行 RNA pulldown 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。基因抑制 SERPINE1 导致 OSCC 细胞活力的降低和 OSCC 细胞凋亡的增殖和升高。根据生物信息学分析，miR-617 包含 SERPINE1 过表达的响应元件，通过 RNA pulldown 和荧光素酶报告基因检测验证。此外，检测到 miR-617 在 OSCC 组织和细胞系中下调，并且与晚期呈负相关。此外，miR-617 模拟物或抑制剂转染可以抑制或促进 SERPINE1 的表达。更重要的是，miR-617 模拟物可以阻断 SERPINE1 过表达对 OSCC 细胞增殖、活力和凋亡的影响。SERPINE1 作为增殖致癌因子在 OSCC 细胞中部分受 miR-167 下调的调节。所以，