LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

• Published in: Cell death & disease Vol. 12; no. 4; p. 331
• Main Authors: Dong, Chen-Hua, Jiang, Tao, Yin, Hang, Song, Hu, Zhang, Yi, Geng, Hao, Shi, Pei-Cong, Xu, Yi-Xin, Gao, Hong, Liu, Lian-Yu, Zhou, Lei, Zhang, Zhao-Hui, Song, Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.03.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 45/91; 631/67; 692/699; 82/80; Animals; Antibodies; Apoptosis; Apoptosis - physiology; Biochemistry; Biomedical and Life Sciences; Cancer; Cell Biology; Cell Culture; Cell cycle; Cell growth; Cell Line, Tumor; Cell proliferation; Chromatin remodeling; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cyclin-dependent kinase inhibitor p21; Cyclin-Dependent Kinase Inhibitor p21 - biosynthesis; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Disease Progression; Epithelium; Female; Gene set enrichment analysis; HCT116 Cells; Heterografts; HT29 Cells; Humans; Immunology; Lamin Type B - metabolism; Life Sciences; Mice; Mice, Nude; Mitosis; Molecular modelling; Transfection; Tumor cell lines; Xenografts
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-03602-1

Colorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.