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
Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Jiangsu, 221002, Xuzhou, China.
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Cell Death Dis. 2021 Mar 29;12(4):331. 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.
结直肠癌是全球第二大常见死因。核纤层蛋白B2（LMNB2）参与染色质重塑以及有丝分裂期间核膜的破裂和重组，这是真核细胞增殖所必需的。然而，LMNB2在结直肠癌（CRC）中的作用尚不清楚。本研究探讨了LMNB2在结直肠癌进展中的生物学功能，并探索了可能的分子机制。我们发现，与配对的非癌组织和正常结直肠上皮相比，LMNB2在原发性结直肠癌组织和细胞系中显著上调。结直肠癌组织中LMNB2的高表达与患者的临床病理特征以及较短的总生存期和无病累积生存期显著相关。功能分析，包括CCK8细胞增殖试验、EdU增殖试验、集落形成分析、裸鼠异种移植、细胞周期和凋亡分析表明，LMNB2在体内和体外通过促进细胞周期进程显著促进细胞增殖。此外，基因集富集分析、荧光素酶报告分析和CHIP分析表明，LMNB2通过调节p21启动子促进细胞增殖，而LMNB2对细胞凋亡没有影响。总之，这些发现不仅表明LMNB2通过调节p21介导的细胞周期进程促进结直肠癌的增殖，还提示了LMNB2作为临床预后标志物和分子治疗靶点的潜在价值。
