Qin Xiang, Dishu Zhou, Xinni Xiang, Xin Le, Chaoqun Deng, Ran Sun, Chunhong Li, Huayang Pang, Jin He, Zeze Zheng, Jun Tang, Weiyan Peng, Xi Peng, Xiaoqian He, Fan Wu, Jingfu Qiu, Yongzhu Xu, Tingxiu Xiang
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引用次数: 1
Abstract
Background: The incidence of colorectal cancer (CRC) has increased in recent years. Identification of accurate tumor markers has become the focus of CRC research. Early and frequent DNA methylation tends to occur in cancer. Thus, identifying accurate methylation biomarkers would improve the efficacy of CRC treatment. Neuroglobin (NGB) is involved in neurological and oncological diseases. However, there are currently no reports on epigenetic regulation involvement of NGB in CRC.
Results: NGB was downregulated or silenced in majority CRC tissues and cell lines. The hypermethylation of NGB was detected in tumor tissue, but no or a very low methylation frequency in normal tissues. Overexpression of NGB induced G2/M phase arrest and apoptosis, suppressed proliferation, migration, invasion in vitro, and inhibited CRC tumor growth and angiogenesis in vivo. Isobaric tag for relative and absolute quantitation (Itraq)-based proteomics identified approximately 40% proteins related to cell-cell adhesion, invasion, and tumor vessel formation in the tumor microenvironment, among which GPR35 was proved critical for NGB-regulated tumor angiogenesis suppression in CRC.
Conclusions: NGB, an epigenetically silenced factor, inhibits metastasis through the GPR35 in CRC. It is expected to grow into a potential cancer risk assessment factor and a valuable biomarker for early diagnosis and prognosis assessment of CRC.
背景:近年来,结直肠癌(CRC)的发病率有所上升。准确识别肿瘤标志物已成为结直肠癌研究的重点。早期和频繁的DNA甲基化往往发生在癌症中。因此,鉴定准确的甲基化生物标志物将提高结直肠癌治疗的疗效。神经红蛋白(NGB)与神经和肿瘤疾病有关。然而,目前还没有关于NGB参与CRC的表观遗传调控的报道。结果:NGB在大多数结直肠癌组织和细胞系中表达下调或沉默。在肿瘤组织中检测到NGB的高甲基化,而在正常组织中没有甲基化或甲基化频率很低。过表达NGB诱导G2/M期阻滞和凋亡,抑制体外增殖、迁移、侵袭,抑制体内CRC肿瘤生长和血管生成。基于Isobaric tag for relative and absolute quantitation (Itraq)的蛋白质组学鉴定出肿瘤微环境中约40%与细胞粘附、侵袭和肿瘤血管形成相关的蛋白质,其中GPR35被证明对ngb调控的CRC肿瘤血管生成抑制至关重要。结论:NGB是一种表观遗传沉默因子,通过GPR35抑制结直肠癌的转移。有望成为一种潜在的癌症风险评估因子,成为CRC早期诊断和预后评估的有价值的生物标志物。
Clinical EpigeneticsBiochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍:
Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.