收稿日期: 2023-05-03
网络出版日期: 2023-09-26
基金资助
江苏省妇幼健康科研项目(F201903);徐州市卫生健康委科研项目(XWRCHT20220039)
Expression of LMNB1 in ovarian cancer and its effect on biological behavior of ovarian cancer cells
Received date: 2023-05-03
Online published: 2023-09-26
目的 探讨层黏连蛋白B1(LMNB1)在卵巢癌组织中的表达情况及其对卵巢癌细胞增殖、迁移和侵袭能力的影响及相关机制。 方法 通过TCGA和GEO数据库分析LMNB1在卵巢癌组织和正常卵巢组织中的表达差异。利用 Kaplan-Meier Plotter 数据库分析LMNB1表达水平与卵巢癌患者预后之间的关系。收集68例新鲜卵巢癌组织标本和27例正常卵巢组织标本,通过免疫组化法检测卵巢癌组织和正常卵巢组织中LMNB1的表达情况,并分析其表达水平与临床病理特征间的关系;慢病毒构建稳定敲低LMNB1的卵巢癌SKOV3细胞系,细胞实验检测LMNB1对卵巢癌SKOV3细胞增殖、迁移和侵袭能力的影响,Western blot实验检测LMNB1对MMP-9、MMP-2、TIMP-1的影响。生物信息学进行GO富集分析和KEGG通路分析,探索LMNB1潜在的生物学功能和信号通路。 结果 数据库分析结果表明LMNB1在卵巢癌上高表达,并且LMNB1的高表达与卵巢癌的不良预后相关(P < 0.05)。免疫组化结果表明卵巢癌组织中的LMNB1蛋白表达高于正常卵巢组织(P < 0.05),LMNB1的表达与卵巢癌患者的FIGO分期、组织学分级有明显相关性(P < 0.05)。敲低LMNB1可以抑制卵巢癌SKOV3细胞的增殖、迁移和侵袭能力(P < 0.05)。富集分析显示与LMNB1共表达基因在卵巢癌中主要参与调控PI3K-AKT、P53通路、细胞周期和凋亡。 结论 LMNB1在卵巢癌中高表达,并可促进卵巢癌SKOV3细胞的恶性生物学行为,其机制可能是通过调控PI3K-AKT、P53通路、细胞周期和凋亡来实现的。
程健祥 , 杜文升 , 魏敏 , 王光慧 . LMNB1在卵巢癌组织中的表达及其对卵巢癌细胞生物学行为的影响[J]. 实用医学杂志, 2023 , 39(16) : 2077 -2084 . DOI: 10.3969/j.issn.1006-5725.2023.16.011
Objective To investigate the expression of lamin B1(LMNB1) in ovarian cancer and its effect on the proliferation, migration and invasion of ovarian cancer cells and mechanism. Methods Expression of LMNB1 in ovarian cancer tissues and normal ovarian tissues was analyzed by TCGA database and GEO database; Kaplan-Meier plotter was used to analyze the effect of LMNB1 mRNA expression on the prognosis of patients with ovarian cancer. Sixty-eight ovarian cancer specimens and twenty-seven normal ovarian tissues were selected. The level of LMNB1 was detected in ovarian cancer tissues and normal tissues by immunohistochemistry, and the relationship between LMNB1 and clinicopathological features was analysed. LMNB1-knockdowned SKOV3 ovarian cancer cell lines were constructed, then the effects of down-expression of LMNB1 on proliferation, migration, and invasion of ovarian cancer cells were detected by CCK-8, colony formation assay, scratch wound healing assay, transwell assay and Edu assay. The expression of MMP2, MMP9, TIMP1 were detected by Western blot after the LMNB1 expression level was knockdowned. Gene Ontology (GO) and Kyoto Encyelopedia of Gene and Genomes(KEGG)were used to enrich the biological functions and signaling pathways of LMNB1 and related proteins. Results The expression of LMNB1 gene in human ovarian cancer tissues was significantly higher than that in normal ovarian tissues(P < 0.05). Patients with high LMNB1 expression had poorer overall survival(P < 0.05). Immunohistochemistry show that the expression level of LMNB1 was significantly upregulated in ovarian cancer tissues(P < 0.05), and was correlated with pathological differentiation and Pathological stage. Silencing LMNB1 expression in SKOV3 cells significantly inhibited its proliferation, migration and invasion ability(P < 0.05). LMNB1 and its co-expressed genes are mainly involved in PI3K-AKT pathway, P53 signaling pathway, cell cycle signaling pathway and cell apoptosis pathway. Conclusion The expression of LMNB1 in ovarian cancer tissues was significantly higher than in normal tissues, and strengthened the proliferation,invasion and migration ability of ovarian cancer cells. The mechanism of LMNB1 in ovarian cancer may be to regulate the activities of PI3K-AKT pathway, P53 signaling pathway, cell cycle signaling pathway and cell apoptosis pathway.
Key words: LMNB1; ovarian cancer; invasion; migration
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