B7-H3 enhances the malignant phenotype of colorectal cancer by activating the Wnt/β-catenin pathway mediated by CYP1B1

IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY
Xingxiang Liu , Jie Ding , Qiumei Zong , Yong Mao
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引用次数: 0

Abstract

Background

Colorectal cancer (CRC) is a prevalent malignancy. Previous studies have identified aberrant expression of Cytochrome P450 1B1 (CYP1B1) in human CRC tissues; however, the exact role and molecular mechanism of CYP1B1 in CRC remain unknown.

Methods

This study initially assessed the expression of CYP1B1 in human colorectal cancer samples and cell lines. Subsequently, siRNA or overexpression plasmid of CYP1B1 was transfected into CaCo-2 or SW480 cells, and cell proliferation, cycle, migration, and invasion were analyzed using CCK8, Colony-formation, Ethynyl-20-deoxyuridine incorporation, flow cytometry, wound healing and transwell assays, and the expression level of CYP1B1 was determined by quantitative real-time polymerase chain reaction and western blotting.

Results

The results indicated that up-regulation of CYP1B1 in CRC samples compared to normal tissues, with its expression level correlating with the local infiltration status. CYP1B1 influenced the proliferation of CRC cells, induced epithelial-mesenchymal transition through the Wnt/β-catenin pathway, thereby promoting cell migration and invasion. Additionally, CYP1B1 expression could be regulated by B7-H3 through the PI3K-AKT pathway.

Conclusions

Those findings suggested that overexpression of CYP1B1 enhances the migration and invasion of human CRC cells by activating the PI3K/Akt signaling pathway through B7-H3.
B7-H3通过激活CYP1B1介导的Wnt/β-catenin通路,增强结直肠癌的恶性表型
结直肠癌(CRC)是一种常见的恶性肿瘤。先前的研究已经发现细胞色素P450 1B1 (CYP1B1)在人类结直肠癌组织中的异常表达;然而,CYP1B1在结直肠癌中的确切作用和分子机制尚不清楚。方法本研究初步评估了CYP1B1在人类结直肠癌样本和细胞系中的表达情况。随后,将siRNA或CYP1B1过表达质粒转染CaCo-2或SW480细胞,采用CCK8、集落形成、乙基-20-脱氧尿苷结合、流式细胞术、伤口愈合和transwell检测细胞增殖、周期、迁移和侵袭,并通过实时定量聚合酶链反应和western blotting检测CYP1B1的表达水平。结果与正常组织相比,结直肠癌组织中CYP1B1表达上调,其表达水平与局部浸润状态相关。CYP1B1影响结直肠癌细胞的增殖,通过Wnt/β-catenin通路诱导上皮-间质转化,从而促进细胞迁移和侵袭。此外,B7-H3可通过PI3K-AKT通路调节CYP1B1的表达。结论CYP1B1的过表达可能通过B7-H3激活PI3K/Akt信号通路,从而促进人结直肠癌细胞的迁移和侵袭。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Tissue & cell
Tissue & cell 医学-解剖学与形态学
CiteScore
3.90
自引率
0.00%
发文量
234
期刊介绍: Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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