Department of Cardiac Thoracic Surgery, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), No.61, Jiefang West Road, Furong District, Changsha, 410000, China.
Appl Biochem Biotechnol. 2022 Jul;194(7):3031-3043. doi: 10.1007/s12010-022-03897-6. Epub 2022 Mar 25.
Lung squamous cell carcinoma (LUSC) is one subtype of non-small-cell lung cancer, whose pathogenesis has not been fully understood. Exploring molecular mechanisms of LUSC helps a lot with the development of LUSC novel therapy. Hence, our study aims to investigate novel molecular mechanisms. Differentially expressed miRNAs and mRNAs were acquired from The Cancer Genome Atlas database. A series of assays were applied to test cell functions, including qRT-PCR to analyze RND1 and miR-4652-5p expression, dual-luciferase reporter gene assay to verify the targeting relationship between these two genes, cell counting kit-8 and colony formation assays to evaluate the ability of LUSC cells to proliferate, transwell to examine the migratory and invasive abilities, and western blot to test expression of RND1 and cell adhesion-related proteins. RND1 was lowly expressed while miR-4652-5p was highly expressed in LUSC cells. The correlation between these two genes was significantly negative and miR-4652-5p could downregulate RND1 expression. Additionally, cellular function assays validated that RND1 suppressed LUSC cells to proliferate, migrate, and invade. Besides, this gene might also affect cell adhesion. Furthermore, rescue assay suggested that miR-4652-5p downregulated RND1 expression to promote the progression of LUSC cells. Together, miR-4652-5p targeted RND1 to modulate cell adhesion and the progression of LUSC cells.
肺鳞状细胞癌（LUSC）是一种非小细胞肺癌，其发病机制尚未完全阐明。探索 LUSC 的分子机制有助于开发 LUSC 的新型治疗方法。因此，我们的研究旨在探讨新的分子机制。从癌症基因组图谱数据库中获得差异表达的 miRNAs 和 mRNAs。应用一系列实验来测试细胞功能，包括 qRT-PCR 分析 RND1 和 miR-4652-5p 的表达、双荧光素酶报告基因实验验证这两个基因的靶向关系、细胞计数试剂盒-8 和集落形成实验评估 LUSC 细胞的增殖能力、Transwell 检测细胞的迁移和侵袭能力，以及 Western blot 检测 RND1 和细胞黏附相关蛋白的表达。在 LUSC 细胞中，RND1 表达水平较低，而 miR-4652-5p 表达水平较高。这两个基因之间的相关性呈显著负相关，miR-4652-5p 可以下调 RND1 的表达。此外，细胞功能实验验证了 RND1 抑制 LUSC 细胞的增殖、迁移和侵袭。此外，该基因可能还会影响细胞黏附。此外，挽救实验表明，miR-4652-5p 通过下调 RND1 表达来促进 LUSC 细胞的进展。总之，miR-4652-5p 通过靶向 RND1 来调节 LUSC 细胞的黏附和进展。
