骨形态发生蛋白 8B (BMP8B) 在胃癌疾病进展中的推定双重作用

Zhiwei Sun, Shuo Cai, Xiangyi Liu, Wen G Jiang, Lin Ye
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引用次数: 0

摘要

背景/目的:骨形态发生蛋白 8B(BMP8B)在胃癌(GC)患者骨髓和原发肿瘤中的表达增加与疾病进展和预后不良有关。然而,由于组蛋白乙酰化,GC 中的表达也有所降低。本研究旨在评估大型胃癌队列中的 BMP8B 转录本水平及其对细胞功能的影响:采用实时 PCR 方法测定了 319 例胃肿瘤中的 BMP8B 转录本,并与 182 例邻近正常组织进行了比较,还在 TCGA 数据库中进行了进一步分析。采用 Kaplan-Meier plotter 分析法评估 BMP8B 与疾病预后的相关性。采用BMP8B基因敲除模型确定BMP8B对GC细胞(HGC27)功能的影响:结果:在TCGA数据库和北京肿瘤医院的数据库中,与邻近正常组织相比,GC组织中BMP8B mRNA水平明显上调,且BMP8B的高表达与预后不良相关。BMP8B很可能参与了GC的分化。与分化良好和中度分化的 GC 样本相比,分化不良的 GC 样本的 BMP8B 表达明显降低。BMP8B敲除抑制了GC细胞的增殖,同时促进了癌细胞的侵袭和迁移:结论:BMP8B在GC中减少,而BMP8B的高表达与预后不良有关。敲除 BMP8B 可抑制 GC 细胞的增殖,促进侵袭和迁移。我们的研究结果表明,BMP8B 在 GC 中发挥着双重作用。
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Putative Dual Roles of Bone Morphogenetic Protein 8B (BMP8B) in Disease Progression of Gastric Cancer.

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.

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