细胞色素可减轻黑色素瘤的恶性程度,但可保护黑色素瘤细胞免于铁变态反应。

IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Molecular medicine reports Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI:10.3892/mmr.2024.13343
Zuquan Zou, Qingyao Yu, Yong Yang, Feng Wang, Pan Zhu, Xiaohong Zhang, Jinjie Zhang
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引用次数: 0

摘要

皮肤恶性黑色素瘤是最具侵袭性和最致命的皮肤癌。目前的黑色素瘤治疗普遍存在两类局限性:不良反应和效率降低。细胞色素(CYGB)是一种铁的六配位球蛋白,在黑色素细胞中含量很高,在黑色素瘤发生过程中经常被表观遗传沉默。本研究旨在探索其作为铁中毒治疗生物标志物的潜在作用。研究发现,CYGB表达缺失的B16F10和A375黑色素瘤细胞对铁色素沉着诱导剂RSL3和厄拉斯汀高度敏感,而CYGB高度富集的G361黑色素瘤细胞对RSL3或厄拉斯汀具有抗性。异位过表达的 CYGB 使 B16F10 和 A375 细胞对 RSL3 或厄拉斯汀产生抗性,并伴随着增殖和上皮-间质转化(EMT)的减少。相比之下,敲除 CYGB 的表达会使 G361 细胞对铁蛋白沉降诱导敏感,但会诱导 G361 细胞的增殖和 EMT 进展。从机理上讲,CYGB诱导的黑色素瘤细胞对铁变态反应的耐受性可能部分与以下因素有关:i) EMT的抑制;ii) 谷胱甘肽过氧化物酶4表达的上调;iii) 易溶铁池的减少。体内研究还表明,CYGB 的过表达使异种移植黑色素瘤对 RSL3 治疗的抵抗力大大增强。基于这些发现,CYGB 是一种潜在的治疗生物标志物,可用于筛选最有可能从铁中毒治疗中获益的黑色素瘤患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cytoglobin attenuates melanoma malignancy but protects melanoma cells from ferroptosis.

Cutaneous malignant melanoma is the most aggressive and the deadliest form of skin cancer. There are two types of limitations which universally exist in current melanoma therapy: Adverse effects and reduced efficiency. Cytoglobin (CYGB), an iron hexacoordinated globin, is highly enriched in melanocytes and frequently epigenetically silenced during melanoma genesis. The present study aimed to explore its potential role as a biomarker for ferroptosis treatment. It was observed that B16F10 and A375 melanoma cells with loss of CYGB expression were highly sensitive to ferroptosis inducers RSL3 and erastin, whereas G361 melanoma cells with highly enriched CYGB were resistant to RSL3 or erastin. Ectopically overexpressed CYGB rendered B16F10 and A375 cells resistant to RSL3 or erastin, accompanied by decreased proliferation and epithelial‑mesenchymal transition (EMT). By contrast, knockdown of CYGB expression made G361 cells sensitive to ferroptosis induction but induced proliferation and EMT progression of G361 cells. Mechanistically, CYGB‑induced resistance of melanoma cells to ferroptosis may have been associated, in part, with i) Suppression of EMT; ii) upregulation of glutathione peroxidase 4 expression; iii) decrease of labile iron pool. In vivo study also demonstrated that CYGB overexpression rendered xenograft melanoma much more resist to RSL3 treatment. Based on these findings, CYGB is a potential therapeutic biomarker to screen the melanoma patients who are most likely benefit from ferroptosis treatment.

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来源期刊
Molecular medicine reports
Molecular medicine reports 医学-病理学
CiteScore
7.60
自引率
0.00%
发文量
321
审稿时长
1.5 months
期刊介绍: Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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