Department of Cardio-Thoracic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.
Comput Math Methods Med. 2021 Jul 8;2021:6248793. doi: 10.1155/2021/6248793. eCollection 2021.
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.
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.
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.
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.
肺鳞状细胞癌（LUSC）是一种全球恶性肿瘤，其发病率和死亡率都很高。本研究主要探讨了一个依赖于 miR-223-5p 的机制，该机制影响 LUSC 细胞的增殖、侵袭和迁移。
从 TCGA 数据库中下载 LUSC 成熟 miRNA 的表达数据和总 RNA 的测序数据。获得差异表达的 mRNA。通过 qRT-PCR、MTT、划痕愈合试验、Western blot 和 Transwell 试验检测 miR-223-5p 在 LUSC 细胞中的作用。Western blot 分析 OTX1 与 JAK/STAT 信号通路的关系。双荧光素酶报告基因检测 miR-223-5p 与 OTX1 的关系。进一步探讨 miR-223-5p 通过 OTX1 调节 LUSC 细胞生物学功能的方式。
发现在 LUSC 组织和细胞中 miR-223-5p 的表达显著降低。过表达 miR-223-5p 可负调控 LUSC 细胞的增殖、侵袭和迁移。在 LUSC 细胞中检测到下游靶基因 OTX1 明显上调。还发现 OTX1 与 miR-223-5p 之间存在负相关。通过 GSEA 分析，OTX1 在 JAK/STAT 信号通路中显著富集并激活该通路。双荧光素酶报告基因实验表明，OTX1 是 LUSC 细胞中 miR-223-5p 的直接分子靶标。挽救实验验证了 miR-223-5p 通过与 OTX1 配对调节 LUSC 细胞的恶性表型。
本研究表明 miR-223-5p 在 LUSC 细胞中低表达。miR-223-5p 通过靶向 OTX1 影响细胞增殖、侵袭和迁移。miR-223-5p 可能成为 LUSC 治疗的新靶点，为未来 LUSC 治疗提供了新的思路。
