CENPB促进肝细胞癌的增殖并受miR-29a直接调控。
CENPB promotes the proliferation of hepatocellular carcinoma and is directly regulated by miR-29a.
发表日期:2023 Nov 02
作者:
Xuyang Wang, Laibang Luo, Youfu Zhang, Gang Liu, Zehong Fang, Zhidan Xu, Xuguang Hu
来源:
Protein & Cell
摘要:
肝细胞癌(HCC)是一个重要的全球健康问题,因为它是第六大常见恶性肿瘤和癌症相关死亡的第三大原因。在本研究中,我们使用 TCGA 和 GEO 数据集分析了 HCC 中着丝粒蛋白 B (CENPB) mRNA 的表达。采用免疫组织化学 (IHC) 测定 490 名 HCC 患者的 CENPB 蛋白水平。我们的研究结果显示,三个数据集中 HCC 组织中 CENPB mRNA 的表达较高。此外,随着病理分期和组织学分级的进展,CENPB表达增加。 CENPB mRNA 和蛋白质水平升高的患者表现出较短的总生存期 (OS) 和无复发生存期 (OS)。值得注意的是,CENPB 蛋白对 I/II 期、AFP 水平低于 400 ng/ml、肿瘤大小小于 5 cm 的患者显示出预后价值。通过对 490 名 HCC 患者进行多元回归分析,我们开发了列线图来预测 1 年、3 年和 5 年 OS 和 RFS。 Hep3B 和 MHCC97 细胞系中 CENPB 的敲低导致细胞增殖和侵袭的显着抑制。此外,生物信息学分析确定 miR-29a 是 CENPB 表达的潜在负调节因子,并通过双荧光素酶报告基因测定进行了验证。总之,我们的研究结果表明 CENPB 可能作为 HCC 的致癌因子,并受 miR-29a 直接调节,凸显了其作为有前景的治疗靶点的潜力。
Hepatocellular carcinoma (HCC) is a significant global health concern as it ranks as the sixth most common malignant tumor and the third leading cause of cancer-related deaths. In this study, we analyzed the expression of centromere protein B (CENPB) mRNA in HCC using TCGA and GEO datasets. Immunohistochemistry (IHC) was performed to determine CENPB protein levels in 490 HCC patients. Our findings revealed higher expression of CENPB mRNA in HCC tissues across the three datasets. Additionally, as the pathological stage and histological grade advanced, CENPB expression increased. Patients with elevated levels of CENPB mRNA and protein demonstrated shorter overall survival (OS) and recurrence-free survival (OS). Notably, CENPB protein showed prognostic value in patients with stage I/II, AFP levels below 400 ng/ml, and tumor size less than 5 cm. Using multivariate regression analysis in 490 HCC patients, we developed nomograms to predict 1-year, 3-year, and 5-year OS and RFS. Knockdown of CENPB in Hep3B and MHCC97 cell lines resulted in significant inhibition of cell proliferation and invasion. Furthermore, bioinformatics analysis identified miR-29a as a potential negative regulator of CENPB expression, which was validated through a dual-luciferase reporter assay. In conclusion, our findings suggest that CENPB may serve as an oncogenic factor in HCC and is directly regulated by miR-29a, highlighting its potential as a promising therapeutic target.