LMNB2 Promotes the Progression of Colorectal Cancer by Silencing p21 Expression
| Autor: | Lei Zhou, Chenhua Dong, Hu Song, Pei-Cong Shi, Tao Jiang, Yi Zhang, Lianyu Liu, Yixin Xu, Hong Gao, Zhao-Hui Zhang, Jun Song, Hang Yin, Hao Geng |
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| Rok vydání: | 2020 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cancer Research Colorectal cancer Immunology Mice Nude Diseases Apoptosis Biology Transfection Chromatin remodeling Article Cellular and Molecular Neuroscience Mice Cell Line Tumor medicine Gene silencing Animals Humans lcsh:QH573-671 Mitosis Cancer Lamin Type B Cell growth lcsh:Cytology Cell Biology Cell cycle medicine.disease HCT116 Cells Cancer research Disease Progression Heterografts Female Colorectal Neoplasms HT29 Cells |
| Zdroj: | Cell Death and Disease, Vol 12, Iss 4, Pp 1-12 (2021) Cell Death & Disease |
| DOI: | 10.21203/rs.3.rs-97868/v1 |
| Popis: | Background: Lamin B2 (LMNB2) is involved in chromatin remodelling and the rupture and reorganization of the nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, there are few reports on the expression and function of LMNB2 in colorectal cancer.Methods: A tissue microarray (TAM) was used to detect the expression of LMNB2 in 226 colorectal cancer tissues and the corresponding adjacent tissues. The CCK-8 colorimetric assay, EdU incorporation analyses, colony formation assays and cell cycle experiments were used to evaluate the effect of LMNB2 on colorectal cancer cell proliferation in vitro, and a mouse tumorigenic model was used to study the effect of LMNB2 on colorectal cancer cells in vivo. The main pathways and genes regulated by LMNB2 were detected by RNA sequencing. Dual-luciferase reporter assays were conducted to test the direct binding between LMNB2 and p21, and ChIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter.Results: The results showed that LMNB2 expression is increased in colorectal cancer tissues. Highly expressed LMNB2 is associated with tumour size and TNM stage. Multivariate Cox analysis showed that LMNB2 can be used as an independent prognostic factor in patients with colorectal cancer. Functional assays indicated that LMNB2 obviously enhanced cell proliferation by promoting cell cycle progression in vitro and in vivo. LMNB2 facilitates cell proliferation via regulating the p21 promoter, whereas LMNB2 had no effect on cell apoptosis in terms of mechanism.Conclusion: LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, indicating the potential value of LMNB2 as a clinical prognostic marker and molecular therapeutic target. |
| Databáze: | OpenAIRE |
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