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WHSC1 promotes wnt/β-catenin signaling in a FoxM1-dependent manner facilitating proliferation, invasion and epithelial-mesenchymal transition in breast cancer
Journal of Receptors and Signal Transduction ( IF 2.8 ) Pub Date : 2020-04-21 , DOI: 10.1080/10799893.2020.1747490
Jinfan Zhang 1 , Jingyu Lu 1 , Yu Chen 1 , Hang Li 1 , Lisheng Lin 1
Affiliation  

Abstract Objectives: Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1) is highly expressed in various malignant tumors. We investigated the correlation and regulatory pathway of WHSC1 in the progression of breast cancer (BC). Methods: The expression and distribution of WHSC1 in the BC tissues and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining. Spearman correlation analysis demonstrated the correlation between WHSC1 high expression level and the clinical characteristics of BC patients. The effects of WHSC1 on the proliferation, apoptosis, migration and invasion of BC cells were analyzed by cell transfection, MTT, colony formation, scratch assay, and transwell. Furthermore, the expression of Forkhead box M1 (FoxM1) and the location of β-catenin were detected by qRT-PCR and western blot. Results: Firstly, WHSC1 expression was up-regulated in BC tissues and cell lines. The high expression of WHSC1 in BC is associated with the tumor size (p = 0.027), metastasis (p = 0.018) and pathological stages (p = 0.025) of the BC patients. The knockdown of WHSC1 inhibited the growth, proliferation migration, invasion and EMT of BC cell lines. Furthermore, WHSC1 could promote the expression of FoxM1 in BC cells and tissues. WHSC1 enhanced the expression of FoxM1, and promoted the nuclear localization of β-catenin, and thus activated the downstream genes expression of Wnt/β-catenin signaling pathway to regulate the development of BC. Conclusion: In summary, our study elucidates the correlation and specific regulatory mechanism between WHSC1 and the progression of BC, thus implying that WHSC1 may function as molecular diagnosis, prognosis and molecular targeted therapy of BC.

中文翻译:

WHSC1 以 FoxM1 依赖性方式促进 wnt/β-catenin 信号传导,促进乳腺癌的增殖、侵袭和上皮间质转化

摘要 目的:Wolf-Hirschhorn 综合征候选基因-1(WHSC1)在多种恶性肿瘤中高表达。我们研究了 WHSC1 在乳腺癌 (BC) 进展中的相关性和调控途径。方法:通过定量逆转录-聚合酶链反应(qRT-PCR)和免疫组织化学染色测定 WHSC1 在 BC 组织和细胞系中的表达和分布。Spearman 相关分析证明 WHSC1 高表达水平与 BC 患者的临床特征之间存在相关性。通过细胞转染、MTT、集落形成、划痕实验和transwell分析WHSC1对BC细胞增殖、凋亡、迁移和侵袭的影响。此外,通过qRT-PCR和蛋白质印迹检测Forkhead box M1(FoxM1)的表达和β-catenin的位置。结果:首先,WHSC1在BC组织和细胞系中表达上调。BC 中 WHSC1 的高表达与 BC 患者的肿瘤大小 (p = 0.027)、转移 (p = 0.018) 和病理分期 (p = 0.025) 相关。WHSC1 的敲低抑制了 BC 细胞系的生长、增殖迁移、侵袭和 EMT。此外,WHSC1 可以促进 FoxM1 在 BC 细胞和组织中的表达。WHSC1通过增强FoxM1的表达,促进β-catenin的细胞核定位,从而激活Wnt/β-catenin信号通路下游基因的表达调控BC的发生发展。结论:总而言之,
更新日期:2020-04-21
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