Background. Lung squamous cell carcinoma (LUSC) features high morbidity and mortality as a worldwide malignant tumor. This study mainly explored a miR-223-5p-dependent mechanism that affected proliferation, invasion, and migration of LUSC cells. Methods. Expression data of mature miRNAs and sequencing data of total RNA of LUSC were downloaded from TCGA database. Differentially expressed mRNAs were obtained. Function of miR-223-5p in LUSC cells was detected by assays like qRT-PCR, MTT, wound healing assay, Western blot, and Transwell assay. Western blot was performed to analyze the relationship between OTX1 and JAK/STAT signaling pathways. Dual-luciferase assay detected the relationship between miR-223-5p and OTX1. The way how miR-223-5p regulated LUSC cell biological functions via OTX1 was further explored. Results. It was noted that miR-223-5p expression in LUSC tissue and cells was significantly reduced. Overexpression of miR-223-5p negatively regulated the proliferation, invasion, and migration of LUSC cells. The downstream target gene OTX1 was detected to be notably elevated in LUSC cells. A negative correlation between OTX1 and miR-223-5p was also found. As analyzed by GSEA, OTX1 was significantly enriched in the JAK/STAT signaling pathway and activated the pathway. Dual-luciferase assay demonstrated that OTX1 was a direct molecular target of miR-223-5p in LUSC cells. Rescue experiment verified that miR-223-5p regulated the malignant phenotypes of LUSC cells by pairing with OTX1. Conclusion. This study indicated that miR-223-5p was lowly expressed in LUSC cells. The impact of miR-223-5p on cell proliferation, invasion, and migration was realized by targeting OTX1. It is likely that miR-223-5p can be a novel target for LUSC treatment, which provides new ideas for future LUSC treatment.

中文翻译：

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miR-223-5p 抑制 OTX1 介导肺鳞状细胞癌细胞的恶性进展

背景。肺鳞状细胞癌（LUSC）是一种发病率和死亡率较高的世界性恶性肿瘤。本研究主要探讨miR-223-5p依赖性影响LUSC细胞增殖、侵袭和迁移的机制。方法。从TCGA数据库下载LUSC成熟miRNA的表达数据和总RNA测序数据。获得差异表达的mRNA。通过 qRT-PCR、MTT、伤口愈合实验、Western blot 和 Transwell 实验等方法检测 LUSC 细胞中 miR-223-5p 的功能。通过Western blot分析OTX1与JAK/STAT信号通路的关系。双荧光素酶检测检测miR-223-5p与OTX1之间的关系。进一步探讨了miR-223-5p如何通过OTX1调节LUSC细胞生物学功能。结果。值得注意的是，LUSC 组织和细胞中的 miR-223-5p 表达显着降低。miR-223-5p 的过表达负向调节 LUSC 细胞的增殖、侵袭和迁移。检测到下游靶基因OTX1在LUSC细胞中显着升高。还发现 OTX1 和 miR-223-5p 之间呈负相关。GSEA 分析显示，OTX1 在 JAK/STAT 信号通路中显着富集并激活该通路。双荧光素酶测定表明 OTX1 是 LUSC 细胞中 miR-223-5p 的直接分子靶标。拯救实验证实miR-223-5p通过与OTX1配对调节LUSC细胞的恶性表型。结论。本研究表明 miR-223-5p 在 LUSC 细胞中低表达。miR-223-5p 对细胞增殖、侵袭和迁移的影响是通过靶向 OTX1 实现的。miR-223-5p很可能成为LUSC治疗的新靶点，为未来LUSC治疗提供新思路。