Obesity and cervical intraepithelial neoplasia: regulation of mitochondrial energy metabolism via the Kisspeptin/GPR54 signaling pathway.

IF 6 3区医学 Q1 CELL BIOLOGY

Cancer & Metabolism Pub Date : 2025-06-18 DOI:10.1186/s40170-025-00398-y

Jiajia Pan, Yuanyuan Chen, Yan Ye, Peipei Li, Feifei Ni, Haizhen He

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引用次数: 0

Abstract

Background: Obesity exacerbates the severity of cervical intraepithelial neoplasia (CIN), potentially through metabolic alterations. This study investigates how the Kisspeptin/GPR54 signaling pathway mediates mitochondrial energy metabolism in obesity-related CIN.

Methods: A clinical analysis of 980 samples was conducted to assess the correlation between Body Mass Index (BMI) and CIN grade. Transcriptomic analysis identified KISS1R as a key gene. Functional assays in cervical cancer (CC) cell lines, including CCK-8, wound healing, and Transwell assays, were used to evaluate the effects of KISS1 modulation. Mitochondrial function was assessed via oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) assays. A high-fat diet-induced CIN mouse model was used to investigate the in vivo effects.

Results: BMI positively correlated with CIN grade, with elevated KISS1R expression in higher CIN grades. Overexpression of KISS1 enhanced CC cell proliferation and migration by reprogramming mitochondrial energy metabolism. In high-fat environments, KISS1 silencing and mitochondrial activator PQQ modulated CC cell behavior. Activation of Kisspeptin/GPR54 in obese CIN mice exacerbated cervical lesions.

Conclusion: The Kisspeptin/GPR54 signaling pathway enhances mitochondrial energy metabolism, promoting obesity-related CIN grade. These findings provide a potential molecular mechanism linking obesity to CC and suggest new therapeutic targets.

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肥胖和宫颈上皮内瘤变：通过Kisspeptin/GPR54信号通路调节线粒体能量代谢

背景：肥胖可能通过代谢改变加重宫颈上皮内瘤变（CIN）的严重程度。本研究探讨Kisspeptin/GPR54信号通路如何介导肥胖相关CIN的线粒体能量代谢。方法：对980例患者进行临床分析，评价身体质量指数（BMI）与CIN分级的相关性。转录组学分析鉴定KISS1R为关键基因。宫颈癌细胞系的功能测定，包括CCK-8、伤口愈合和Transwell测定，用于评估KISS1调节的作用。通过耗氧率（OCR）和细胞外酸化率（ECAR）测定评估线粒体功能。采用高脂饮食诱导的CIN小鼠模型研究其体内效应。结果：BMI与CIN分级呈正相关，较高CIN分级KISS1R表达升高。KISS1过表达通过重编程线粒体能量代谢增强CC细胞增殖和迁移。在高脂肪环境中，KISS1沉默和线粒体激活因子PQQ调节CC细胞的行为。Kisspeptin/GPR54在肥胖CIN小鼠中的激活加重了宫颈病变。结论：Kisspeptin/GPR54信号通路增强线粒体能量代谢，促进肥胖相关CIN分级。这些发现提供了将肥胖与CC联系起来的潜在分子机制，并提出了新的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer & Metabolism Multiple-

自引率

1.70%

发文量

审稿时长

14 weeks

期刊介绍： Cancer & Metabolism welcomes studies on all aspects of the relationship between cancer and metabolism, including: -Molecular biology and genetics of cancer metabolism -Whole-body metabolism, including diabetes and obesity, in relation to cancer -Metabolomics in relation to cancer; -Metabolism-based imaging -Preclinical and clinical studies of metabolism-related cancer therapies.