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骨形态发生蛋白8B(BMP8B)在胃癌疾病进展中的潜在双重作用

Putative Dual Roles of Bone Morphogenetic Protein 8B (BMP8B) in Disease Progression of Gastric Cancer.

作者信息

Sun Zhiwei, Cai Shuo, Liu Xiangyi, Jiang Wen G, Ye Lin

机构信息

Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, U.K.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), The VIP-II Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital & Institute, Beijing, P.R. China.

出版信息

Cancer Diagn Progn. 2024 Sep 1;4(5):567-578. doi: 10.21873/cdp.10365. eCollection 2024 Sep-Oct.

Abstract

BACKGROUND/AIM: Increased expression of bone morphogenetic protein 8B (BMP8B) in bone marrow and primary tumors of patients with gastric cancer (GC) is associated with disease progression and poor prognosis. However, a reduced expression has also been seen in GCs due to histone acetylation. This study aimed to evaluate BMP8B transcript levels in a large GC cohort and its impact on cellular functions.

MATERIALS AND METHODS

BMP8B transcripts were determined in 319 gastric tumors and compared with 182 adjacent normal tissues using real time PCR, with a further analysis conducted in the TCGA database. Kaplan-Meier plotter analysis was performed to evaluate the correlation between BMP8B and prognosis of the disease. BMP8B knockdown model was employed to determine the effect of BMP8B on the function of GC cells (HGC27).

RESULTS

BMP8B mRNA levels were significantly up-regulated in the GC tissues compared with adjacent normal tissues in both TCGA database and our own database from Beijing Cancer Hospital, and high BMP8B expression was associated with poor prognosis. BMP8B is most likely to be involved in the differentiation of GC. Poorly differentiated GC samples presented a significantly reduced BMP8B expression in relation to well-differentiated and moderately differentiated GC. BMP8B knockdown inhibited proliferation of GC cells, while promoted invasion and migration of cancer cells.

CONCLUSION

BMP8B was reduced in GCs, whereas higher BMP8B expression was associated with poor prognosis. BMP8B knockdown inhibited proliferation of GC cells, and promoted invasion and migration. Our results suggest that BMP8B plays dual roles in GC.

摘要

背景/目的:胃癌(GC)患者骨髓和原发性肿瘤中骨形态发生蛋白8B(BMP8B)表达增加与疾病进展和预后不良相关。然而,由于组蛋白乙酰化,在胃癌中也观察到BMP8B表达降低。本研究旨在评估一大群胃癌患者中BMP8B转录水平及其对细胞功能的影响。

材料与方法

使用实时PCR测定319例胃肿瘤中BMP8B转录本,并与182例相邻正常组织进行比较,并在TCGA数据库中进行进一步分析。采用Kaplan-Meier绘图分析评估BMP8B与疾病预后之间的相关性。采用BMP8B敲低模型确定BMP8B对胃癌细胞(HGC27)功能的影响。

结果

在TCGA数据库以及我们来自北京肿瘤医院的数据库中,与相邻正常组织相比,胃癌组织中BMP8B mRNA水平显著上调,且BMP8B高表达与预后不良相关。BMP8B很可能参与胃癌的分化。与高分化和中分化胃癌相比,低分化胃癌样本中BMP8B表达显著降低。BMP8B敲低抑制胃癌细胞增殖,同时促进癌细胞侵袭和迁移。

结论

胃癌中BMP8B表达降低,而较高的BMP8B表达与预后不良相关。BMP8B敲低抑制胃癌细胞增殖,并促进侵袭和迁移。我们的结果表明BMP8B在胃癌中发挥双重作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69d2/11372696/2d014aa5d0c0/cdp-4-569-g0001.jpg

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