在三维培养系统中,TET2 介导的甲基化重构对 A2058 黑色素瘤细胞对基质硬度敏感性的影响。

IF 3.5 3区 生物学 Q3 CELL BIOLOGY Experimental cell research Pub Date : 2024-09-01 Epub Date: 2024-08-24 DOI:10.1016/j.yexcr.2024.114224
Zhizhong Shen , Zixian Liu , Meng Li , Lu Han , Jianming Wang , Xunwei Wu , Shengbo Sang
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引用次数: 0

摘要

基质硬度是肿瘤微环境中的一个关键因素,影响着肿瘤的进展和发展。TET2对黑色素瘤的表观遗传调控至关重要,与痣和薄黑色素瘤相比,晚期黑色素瘤中的TET2明显减少。然而,目前还不清楚TET2如何介导基质硬度对黑色素瘤细胞的影响。本研究利用 A2058 细胞系和制备的不同硬度的胶原水凝胶来评估 TET2 过表达(TET2OE)和突变(TET2M)黑色素瘤细胞的活性、增殖和侵袭。A2058 黑色素瘤细胞的活力和侵袭力随着基质硬度的增加而降低,TET2OE 细胞受到的影响比 TET2M 细胞更明显。甲基化分析表明,TET2 决定基因甲基化水平,从而影响细胞与基质的相互作用。转录组分析证实,TET2 促进了基质硬度对黑色素瘤细胞命运的影响。这项研究为黑色素瘤的治疗提供了前景广阔的方向和机会。
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Effects of TET2-mediated methylation reconstruction on A2058 melanoma cell sensitivity to matrix stiffness in a 3D culture system

Matrix stiffness is a crucial factor in the tumor microenvironment, impacting tumor progression and development. TET2 is vital for epigenetic regulation in melanoma and is significantly reduced in advanced melanomas compared with nevi and thin melanomas. However, it is unclear how TET2 mediates the effect of matrix stiffness on melanoma cells. This study utilized A2058 cell lines and prepared different stiffness collagen hydrogels to evaluate TET2 overexpression (TET2OE) and mutant (TET2M) melanoma cells' activity, proliferation, and invasion. A2058 melanoma cells' viability and invasion decreased with increased matrix stiffness, with TET2OE cells experiencing a more significant impact than TET2M cells. Methylation analysis revealed that TET2 determines gene methylation levels, influencing cell-ECM interactions. Transcriptome analysis confirmed that TET2 promotes matrix stiffness's effect on melanoma cell fate. This research provides promising directions and opportunities for melanoma treatment.

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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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