Serinc2 Drives the Progression of Cervical Cancer Through Regulating Myc Pathway

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2024-10-17 DOI:10.1002/cam4.70296

Xiaoping Wang, Chen Jiang, Qing Li

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引用次数: 0

Abstract

Background

As one of the most common malignancies, cervical cancer (CC) seriously affects women's health. This study aimed to investigate the biological function of Serinc2 in CC.

Methods

Serinc2 expression was surveyed utilizing immunohistochemistry, western blot, and qRT-PCR. CC cell viability, invasion, proliferation, migration, and apoptosis, were detected via CCK-8, Transwell assay, colony formation, wound healing assay, and flow cytometry. Glucose consumption, lactate production, and ATP levels were determined by the corresponding kit. The protein expression of c-Myc, PDK1, HK2, PFKP, LDHA, Snail, Vimentin, N-cadherin, and E-cadherin was detected via western blot. The interaction between the promoter of PFKP and Myc was confirmed through luciferase reporter assay and Chip assay. In vivo, to evaluate the function of Serinc2 on tumor growth, a xenograft mouse model was used.

Results

In CC tissues and cells, Serinc2 was upregulated. In CC cells, knockdown of Serinc2 suppressed cell invasion, proliferation, migration, decreased the expression of Snail, Vimentin, N-cadherin, HK2, PFKP, LDHA, and PDK1, increased E-cadherin expression, reduced glucose consumption and the production of lactate and ATP, and induced cell apoptosis; Serinc2 overexpression led to the opposite results. Mechanically, Serinc2 promoted Myc expression, and Myc induced PFKP expression. Furthermore, overexpressed Myc abolished the inhibitive influences of Serinc2 knockdown on the malignant behaviors of CC cells. Additionally, knockdown of Serinc2 inhibited tumor growth and reduced the protein expression of c-Myc, PFKP, LDHA, and PDK1 in vivo.

Conclusions

Knockdown of Serinc2 inhibited the malignant progression of CC, which was achieved via Myc pathway. Our study provides novel insight into CC pathogenesis.

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Serinc2 通过调控 Myc 通路驱动宫颈癌进展

背景宫颈癌（CC）是最常见的恶性肿瘤之一，严重影响妇女的健康。本研究旨在探讨 Serinc2 在宫颈癌中的生物学功能。方法通过免疫组化、Western 印迹和 qRT-PCR 检测 Serinc2 的表达。通过 CCK-8、Transwell 试验、集落形成、伤口愈合试验和流式细胞术检测 CC 细胞的活力、侵袭、增殖、迁移和凋亡。葡萄糖消耗、乳酸生成和 ATP 水平由相应的试剂盒测定。c-Myc, PDK1, HK2, PFKP, LDHA, Snail, Vimentin, N-cadherin和E-cadherin的蛋白表达通过Western印迹检测。通过荧光素酶报告实验和芯片实验证实了 PFKP 启动子与 Myc 之间的相互作用。在体内，为了评估 Serinc2 对肿瘤生长的作用，使用了异种移植小鼠模型。结果在CC组织和细胞中，Serinc2被上调。在CC细胞中，敲除Serinc2可抑制细胞的侵袭、增殖和迁移，降低Snail、Vimentin、N-cadherin、HK2、PFKP、LDHA和PDK1的表达，增加E-cadherin的表达，减少葡萄糖的消耗以及乳酸和ATP的产生，诱导细胞凋亡；过表达Serinc2则导致相反的结果。从机制上看，Serinc2 促进了 Myc 的表达，而 Myc 又诱导了 PFKP 的表达。此外，过表达的Myc消除了Serinc2敲除对CC细胞恶性行为的抑制作用。此外，敲除 Serinc2 可抑制肿瘤生长，并降低 c-Myc、PFKP、LDHA 和 PDK1 在体内的蛋白表达。结论敲除Serinc2可抑制CC的恶性进展，而这是通过Myc通路实现的。我们的研究为CC的发病机制提供了新的见解。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.