SOX2 promotes the glycolysis process to accelerate cervical cancer progression by regulating the expression of HK2

IF 2.3 4区 生物学 Q4 CELL BIOLOGY Acta histochemica Pub Date : 2025-01-16 DOI:10.1016/j.acthis.2025.152230
Ting Wang, Ruoan Jiang, Xueling Tang, Yingsha Yao, Peiyue Jiang
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Abstract

Background

Cervical cancer is a major health burden in females worldwide, available studies indicated that sex-determining region Y-box 2 (SOX2) is closely related to the malignant phenotypes of multiple cancers including cervical cancer. However, the underlying mechanisms were blurred.

Experimental Procedures

A bioinformatics analysis was conducted to investigate the clinical correlation between SOX2 and cervical cancer. Transient transfection and lentivirus infection were utilized to achieve overexpression and knockdown of SOX2, respectively. The role of SOX2 in cervical cancer was confirmed by transwell and colony-forming assays. Immunoblot, dual-luciferase reporter, chromatin immunoprecipitation (ChIP), and biochemical experiments were employed. In addition, the xenograft models and immunohistochemistry (IHC) experiments were performed to validate the findings in vivo.

Results

The expression of SOX2 was significantly positively associated with the cell migration, invasion, and colony-forming abilities of cervical cancer cells. The following immunoblots revealed that the SOX2-induced malignant phenotypes might be related to the glycolysis process, since overexpressing SOX2 significantly promoted the hexokinase 2 (HK2) and glucose transporter-1 (GLUT1) expression, and increased the content of glucose and lactic acid. The further dual-luciferase reporter and ChIP experiments confirmed a binding relationship between SOX2 and HK2 promoter. More importantly, overexpressing SOX2 promoted tumor growth concomitant with a hyper-expression of HK2 and GLUT1 in xenograft tumor tissues, yet the treatment of glycolysis inhibitor significantly reversed those outcomes.

Conclusion

SOX2 promotes the malignant progression of cervical cancer by facilitating glycolysis.
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SOX2通过调节HK2的表达促进糖酵解过程,从而加速宫颈癌的进展。
背景:宫颈癌是全球女性的主要健康负担,现有研究表明,性别决定区Y-box 2 (SOX2)与包括宫颈癌在内的多种癌症的恶性表型密切相关。然而,潜在的机制是模糊的。实验方法:通过生物信息学分析探讨SOX2与宫颈癌的临床相关性。利用瞬时转染和慢病毒感染分别实现SOX2的过表达和低表达。通过transwell和集落形成试验证实了SOX2在宫颈癌中的作用。采用免疫印迹、双荧光素酶报告基因、染色质免疫沉淀(ChIP)和生化实验。此外,通过异种移植物模型和免疫组化(IHC)实验验证了体内研究结果。结果:SOX2的表达与宫颈癌细胞的迁移、侵袭和集落形成能力呈显著正相关。随后的免疫印迹显示,SOX2诱导的恶性表型可能与糖酵解过程有关,过表达SOX2可显著促进己糖激酶2 (HK2)和葡萄糖转运蛋白-1 (GLUT1)的表达,增加葡萄糖和乳酸的含量。进一步的双荧光素酶报告基因和ChIP实验证实了SOX2和HK2启动子之间的结合关系。更重要的是,在异种移植肿瘤组织中,过表达SOX2促进肿瘤生长,同时高表达HK2和GLUT1,而糖酵解抑制剂的治疗显著逆转了这些结果。结论:SOX2通过促进糖酵解促进宫颈癌恶性进展。
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来源期刊
Acta histochemica
Acta histochemica 生物-细胞生物学
CiteScore
4.60
自引率
4.00%
发文量
107
审稿时长
23 days
期刊介绍: Acta histochemica, a journal of structural biochemistry of cells and tissues, publishes original research articles, short communications, reviews, letters to the editor, meeting reports and abstracts of meetings. The aim of the journal is to provide a forum for the cytochemical and histochemical research community in the life sciences, including cell biology, biotechnology, neurobiology, immunobiology, pathology, pharmacology, botany, zoology and environmental and toxicological research. The journal focuses on new developments in cytochemistry and histochemistry and their applications. Manuscripts reporting on studies of living cells and tissues are particularly welcome. Understanding the complexity of cells and tissues, i.e. their biocomplexity and biodiversity, is a major goal of the journal and reports on this topic are especially encouraged. Original research articles, short communications and reviews that report on new developments in cytochemistry and histochemistry are welcomed, especially when molecular biology is combined with the use of advanced microscopical techniques including image analysis and cytometry. Letters to the editor should comment or interpret previously published articles in the journal to trigger scientific discussions. Meeting reports are considered to be very important publications in the journal because they are excellent opportunities to present state-of-the-art overviews of fields in research where the developments are fast and hard to follow. Authors of meeting reports should consult the editors before writing a report. The editorial policy of the editors and the editorial board is rapid publication. Once a manuscript is received by one of the editors, an editorial decision about acceptance, revision or rejection will be taken within a month. It is the aim of the publishers to have a manuscript published within three months after the manuscript has been accepted
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