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

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Abstract

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.

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Data Availability

The data used to support the findings of this study are included within the article. The data and materials in the current study are available from the corresponding author on reasonable request.

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  1. Cardiothoracic Surgery Department, The First People’s Hospital of Fuyang, No. 429, Beihuan Road, Fuchun Street, Fuyang District, Hangzhou, 311400, Zhejiang, China

    Bin Bao, Xiaojun Yu & Wujun Zheng

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  1. Bin Bao
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12033_2022_465_MOESM1_ESM.tif

Supplementary Fig. 1 LUAD malignant progression was suppressed by silencing CCNB1. A: CCNB1 level in H1299 cells; B: The proliferation ability of H1299 cells; C: The invasion of H1299 cells (100×); D: The migration ability of H1299 cells (40×); E: The cell cycle of H1299. The cell grouping settings were as follows: H1299 cells with si-NC and si-CCNB1. * denotes p<0.05 (TIF 3302 kb)

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Bao, B., Yu, X. & Zheng, W. MiR-139-5p Targeting CCNB1 Modulates Proliferation, Migration, Invasion and Cell Cycle in Lung Adenocarcinoma. Mol Biotechnol 64, 852–860 (2022). https://doi.org/10.1007/s12033-022-00465-5

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