MiR-139-5p Targeting CCNB1 Modulates Proliferation, Migration, Invasion and Cell Cycle in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) is the most frequent histological subtype of non-small cell lung cancer. Cyclin B1 (CCNB1) is the vital initiator and controller of mitosis. Studies have indicated that CCNB1 overexpression is closely associated with cell proliferation and tumorigenesis in many cancers. Thus, discovery of molecular mechanism of CCNB1 in LUAD is conducive to developing new diagnostic or therapeutic targets for LUAD. We acquired mature miRNA and mRNA expression information of LUAD from TCGA database, as well as related clinical data. CCNB1 expression in normal and LUAD tissue was analyzed. Relationship between CCNB1 and patient's survival and clinical stage was analyzed. Upstream regulatory gene miRNA of CCNB1 was predicted. qRT-PCR and western blot examined expression levels of CCNB1 and miR-139-5p in cells. CCK-8 tested cell proliferation. Scratch healing and Transwell determined cell migration and invasion. Flow cytometry analyzed the cell cycle. Dual-luciferase verified targeting relationship between the two genes. Compared to controls, CCNB1 expression was prominently high in LUAD patient samples, and associated with advanced tumor stages and shorter overall survival. MiR-139-5p expressed an evidently negative correlation with CCNB1 and was predicted to target CCNB1. MiR-139-5p mimics reduced CCNB1 mRNA and protein expression, and suppressed luciferase activity in a target-specific manner, as confirmed by a control construct with a mutated miR-139-5p binding site. CCNB1 overexpression fostered progression of LUAD cells. Mechanistically, miR-139-5p might negatively regulate CCNB1 in LUAD, thereby suppressing cell proliferation, migration, invasion and cell cycle.

Automated summary

This study found that overexpression of CCNB1 is associated with tumor progression and shorter overall survival in lung adenocarcinoma (LUAD). It also discovered that miR-139-5p may negatively regulate CCNB1 to suppress proliferation, migration, and invasion of LUAD cells.