转录组与蛋白质组联合分析筛选肾上腺醛固酮瘤的核心致病基因及其生物学功能研究

doi:10.11958/20260728

天津医药 ›› 2026, Vol. 54 ›› Issue (9): 897-901.doi: 10.11958/20260728

• 细胞与分子生物学 • 下一篇

转录组与蛋白质组联合分析筛选肾上腺醛固酮瘤的核心致病基因及其生物学功能研究

周颖¹^,²(), 董文静², 孙迪², 宋凌云², 薛哲², 庞萍², 杨国庆²^,^△()

¹ 解放军医学院研究生院（邮编100039）
² 解放军总医院海南医院内分泌科（邮编100039）

收稿日期:2026-03-17 修回日期:2026-06-07 出版日期:2026-09-15 发布日期:2026-09-14
通讯作者: ^△E-mail：endocrine301@126.com
作者简介:周颖（1994），女，硕士在读，主要从事内分泌与代谢性疾病方面研究。E-mail：2637129761@qq.com
基金资助:
海南省重点研发计划(ZDYF2022SHFZ103);国家重点研发计划(2022YFC2505300);国家重点研发计划(2022YFC2505301)

Screening and functional validation of core pathogenic genes in aldosterone-producing adenoma based on integrated transcriptomic and proteomic analysis

ZHOU Ying¹^,²(), DONG Wenjing², SUN Di², SONG Lingyun², XUE Zhe², PANG Ping², YANG Guoqing²^,^△()

¹ Graduate School of Chinese PLA Medical School, Beijing 100039, China
² Department of Endocrinology, Hainan Hospital of Chinese People's Liberation Army General Hospital, Beijing 100039, China

Received:2026-03-17 Revised:2026-06-07 Published:2026-09-15 Online:2026-09-14
Contact: ^△E-mail: endocrine301@126.com

周颖, 董文静, 孙迪, 宋凌云, 薛哲, 庞萍, 杨国庆. 转录组与蛋白质组联合分析筛选肾上腺醛固酮瘤的核心致病基因及其生物学功能研究[J]. 天津医药, 2026, 54(9): 897-901.

ZHOU Ying, DONG Wenjing, SUN Di, SONG Lingyun, XUE Zhe, PANG Ping, YANG Guoqing. Screening and functional validation of core pathogenic genes in aldosterone-producing adenoma based on integrated transcriptomic and proteomic analysis[J]. Tianjin Medical Journal, 2026, 54(9): 897-901.

摘要/Abstract

摘要：

目的基于转录组与蛋白质组联合分析筛选肾上腺醛固酮瘤（APA）的核心致病基因并验证其生物学功能。方法收集APA组织及肾上腺无功能腺瘤对照组织各3例，同步进行全转录组测序（RNA-seq）与定量蛋白质组学检测。基于转录组与蛋白质组的联合分析，筛选差异表达基因与差异表达蛋白，并通过功能富集分析识别核心通路及关键分子。进一步通过体外细胞实验，采用过表达与沉默技术调控脂肪酸合酶（FASN）表达，检测细胞增殖率、腺苷三磷酸（ATP）含量及醛固酮合成酶（CYP11B2）蛋白的表达。结果共鉴定到10 705个可定量转录本与3 288个可定量蛋白，其中907个分子为两组学共同覆盖。差异分析显示，APA中转录与蛋白水平同步上调的分子共167个，协同下调的分子共213个。功能富集分析表明，协同上调分子显著富集于脂肪酸生物合成、过氧化物酶体增殖物激活受体（PPAR）信号通路及胆固醇代谢等脂代谢相关通路，其中脂肪酸生物合成通路富集显著性最高。进一步筛选出在核心通路中共同富集的10个关键分子，其中FASN作为脂肪酸合成的限速酶，在APA中信使核糖核酸（mRNA）与蛋白水平均显著上调。过表达FASN显著促进细胞增殖（P<0.01），降低ATP含量（P<0.01），并上调CYP11B2蛋白表达（P<0.01）；而沉默FASN则呈现相反结果（P<0.01）。结论 FASN作为脂肪酸合成通路的关键限速酶，可促进肿瘤细胞增殖及醛固酮合成关键酶表达，可能参与APA的发病。

关键词: 醛固酮增多症, 转录组, 蛋白质组, 脂肪酸合酶, 细胞增殖, 脂肪酸代谢

Abstract:

Objective To identify key pathogenic genes in aldosterone-producing adenoma (APA) and validate their biological functions through integrated transcriptomic and proteomic analysis. Methods Three samples each of APA tissue and control tissue from non-functioning adrenal adenomas were collected, and whole-transcriptome sequencing (RNA-seq) and quantitative proteomics were performed simultaneously. Based on integrated transcriptomic and proteomic analysis, differentially expressed genes and proteins were identified, and core pathways and key molecules were identified through functional enrichment analysis. Furthermore, in vitro cellular experiments were conducted using overexpression and silencing techniques to regulate fatty acid synthase (FASN) expression, and cell proliferation rates, adenosine triphosphate (ATP) levels, and the expression of aldosterone synthase (CYP11B2) protein were assessed. Results A total of 10 705 quantifiable transcripts and 3 288 quantifiable proteins were identified, of which 907 molecules were common to both omics datasets. Differential analysis revealed that 167 molecules were upregulated at both transcriptional and protein levels in APA, whilst 213 molecules were downregulated in a coordinated manner. Functional enrichment analysis indicated that the synergistically up-regulated molecules were significantly enriched in lipid metabolism-related pathways, such as fatty acid biosynthesis, the peroxisome proliferator-activated receptor (PPAR) signalling pathway and cholesterol metabolism, with the fatty acid biosynthesis pathway showing the highest level of enrichment. Further screening identified 10 key molecules commonly enriched across these core pathways; among these, FASN—the rate-limiting enzyme in fatty acid synthesis—was significantly upregulated in APA at both the messenger RNA (mRNA) and protein levels. Overexpression of FASN significantly promoted cell proliferation (P<0.01), reduced ATP production (P<0.01), and upregulated CYP11B2 protein expression (P<0.01). In contrast, silencing of FASN produced the opposite results (P<0.01). Conclusion As a key rate-limiting enzyme in the fatty acid synthesis pathway, FASN promotes tumour cell proliferation and the expression of a key enzyme involve in aldosterone synthesis, and may be involved in the pathogenesis of APA.

Key words: hyperaldosteronism, transcriptome, proteome, fatty acid synthase, cell proliferation, fatty acid metabolism

中图分类号:

R318.15，R736

图/表 5

图1 APA与NFALs组织的转录组-蛋白质组联合分析的质量检测转录组（绿色）与蛋白质组（蓝色）检测分子的表达丰度分布直方图。

Fig.1 Quality test for integrated transcriptomic and proteomic analysis of APA and NFALs

图2 转录组与蛋白质组共同上调分子的KEGG通路富集分析及GO功能富集分析 A：转录组与蛋白质组共同上调分子的KEGG通路富集分析气泡图；B：转录组与蛋白质组共同上调分子的GO功能富集分析结果。

Fig.2 KEGG pathway and GO function enrichment analysis of upregulated genes in transcriptomic and proteomic analysis

图3 转染后各组细胞增殖曲线 n=3，F24 h=8.011，F48 h =71.195，F72 h =166.502，F96 h=326.075，均P<0.01。

Fig.3 Proliferation curves of transfected cells of each group

图4 转染后各组细胞ATP含量 A—E分别为空白组、空白质粒组、FASN过表达质粒组、siRNA阴性对照组、FASN-siRNA组。a与空白质粒组相比，b与siRNA阴性对照组相比，P<0.05。

Fig.4 ATP content of transfected cells of each group

图5 转染后各组细胞FASN、CYP11B2蛋白表达水平 A：Western blot检测各组FASN、CYP11B2蛋白表达；1—5分别为空白组、空白质粒组、FASN过表达质粒组、siRNA阴性对照组、FASN-siRNA组。B：各组FASN、CYP11B2蛋白表达柱状图；a与空白质粒组相比，b与siRNA阴性对照组相比，P<0.05；Ⅰ—Ⅴ分别为空白组、空白质粒组、FASN过表达质粒组、siRNA阴性对照组、FASN-siRNA组。

Fig.5 Expression levels of FASN, CYP11B2 in transfected cells of each group

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转录组与蛋白质组联合分析筛选肾上腺醛固酮瘤的核心致病基因及其生物学功能研究

Screening and functional validation of core pathogenic genes in aldosterone-producing adenoma based on integrated transcriptomic and proteomic analysis

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