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北京大学学报（医学版） ›› 2026, Vol. 58 ›› Issue (2): 393-398. doi: 10.19723/j.issn.1671-167X.2026.02.026

• 技术方法 • 上一篇    下一篇

肾透明细胞癌FABP6基因长转录本的表达及意义

殷昊明1,*, 王子杰1,*, 舒帆1, 张展奕1, 梁会2,*(), 张树栋1,*()   

  1. 1. 北京大学第三医院泌尿外科，北京 100191
    2. 北京大学基础医学院病理学系，北京 100191
  • 收稿日期:2024-03-15 出版日期:2026-04-18 发布日期:2026-01-12
  • 通讯作者: 梁会, 张树栋
  • 作者简介:

    *These authors contributed equally to this work

  • 基金资助:
    国家自然科学基金(82273389); 北京市自然科学基金(7232212)

Expression and significance of the FABP6 long transcript in clear cell renal cell carcinoma

Haoming YIN1, Zijie WANG1, Fan SHU1, Zhanyi ZHANG1, Hui LIANG2,*(), Shudong ZHANG1,*()   

  1. 1. Department of Urology, Peking University Third Hospital, Beijing 100191, China
    2. Department of Pathology, Peking University School of Basic Medical Sciences, Beijing 100191, China
  • Received:2024-03-15 Online:2026-04-18 Published:2026-01-12
  • Contact: Hui LIANG, Shudong ZHANG
  • Supported by:
    the National Natural Science Foundation of China(82273389); Beijing Natural Science Foundation(7232212)

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摘要：

目的: 探讨脂肪酸结合蛋白6(fatty acid binding protein 6，FABP6)基因长转录本在肾透明细胞癌(clear cell renal cell carcinoma，ccRCC)中的表达情况及其与肿瘤生物学行为的关系，进一步分析其作为潜在生物标志物和治疗靶点的可能性。方法: 通过基因表达汇编(Gene Expression Omnibus，GEO)和癌症基因组图谱(The Cancer Genome Atlas，TCGA)数据库进行生物信息学分析后，筛选得到与ccRCC发生发展和预后相关的FABP6基因，并通过实验进一步确认其长短转录本的存在情况及表达模式。利用实时荧光定量逆转录PCR(reverse transcription quantitative real-time PCR，RT-qPCR)和蛋白免疫印迹实验检测FABP6基因长短转录本在ccRCC细胞系和组织样本中的表达水平差异。构建FABP6基因长转录本过表达和敲低的ccRCC细胞系，并分别通过5-乙炔基-2’-脱氧尿苷(5-ethynyl-2’-deoxyuridine, EdU)增殖实验和克隆形成实验，评估FABP6基因长转录本对ccRCC细胞增殖能力的影响。结果: 生物信息学数据库分析显示，FABP6基因在ccRCC细胞系和组织样本中的表达高于其正常对照细胞和组织样本(P=0.02)，并且其长转录本为主要表达形式(P=0.02)。RT-qPCR和蛋白免疫印迹实验结果进一步证实，FABP6基因长转录本在ccRCC细胞系769P、A498、CAKI1、OSRC2、786O等中的表达水平高于短转录本。体外功能实验中，过表达FABP6基因长转录本促进ccRCC细胞的增殖能力；相反，敲低FABP6基因长转录本显著抑制ccRCC细胞的增殖能力，提示FABP6基因长转录本可能通过驱动细胞周期进程或调控相关增殖信号通路，在ccRCC的发生发展中扮演了癌基因样的促进作用。结论: 系统报道了FABP6基因长转录本在ccRCC中特异性高表达，并通过功能增益和功能缺失实验证实了其促进ccRCC细胞增殖的关键作用，揭示了FABP6基因，尤其是其长转录本在ccRCC恶性进展中的重要新功能。

关键词: 肾透明细胞癌, FABP6基因, 增殖

Abstract:

Objective: To investigate the expression of the fatty acid binding protein 6 (FABP6) long transcript in clear cell renal cell carcinoma (ccRCC), its correlation with tumor biological behavior, and further analyze its potential as a biomarker and therapeutic target. Methods: Following bioinformatics analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, the FABP6 gene associated with ccRCC development and prognosis was screened. The existence and expression patterns of FABP6 long and short transcripts were further confirmed experimentally. In the experimental section, reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot were used to detect the differential expression levels of the FABP6 long and short transcripts in ccRCC cell lines and tissue samples. ccRCC cell lines with overexpression and knockdown of the FABP6 long transcript were constructed. The impact of the FABP6 long transcript on the proliferation capacity of ccRCC cells was assessed using the 5-ethynyl-2'-deoxyuridine proliferation assay and the colony formation assay, respectively. Results: Bioinformatics database analysis revealed that the expression of the FABP6 gene was higher in ccRCC cell lines and tissue samples compared with their normal counterparts (P=0.02), with FABP6 long transcript being the predominant form (P=0.02). RT-qPCR and Western blot results further confirmed that the expression level of the FABP6 long transcript was higher than that of the FABP6 short transcript in ccRCC cell lines such as 769P, A498, CAKI1, OSRC2, and 786O. In in vitro functional experiments, overexpression of the FABP6 long transcript promoted the proliferation of ccRCC cells. Conversely, knockdown of the FABP6 long transcript significantly inhibited the proliferation of ccRCC cells. This suggested that the FABP6 long transcript might play an oncogenic role in the development and progression of ccRCC, potentially by driving cell cycle progression or regulating related proli-ferative signaling pathways. Conclusion: This study systematically reports the specific high expression of the FABP6 long transcript in ccRCC. Gain-of-function and loss-of-function experiments confirmed its crucial role in promoting ccRCC cell proliferation. This reveals an important new function of the FABP6 gene, particularly FABP6 long transcript, in the malignant progression of ccRCC.

Key words: Clear cell renal cell carcinoma, FABP6 gene, Proliferation

中图分类号: 

  • R737.1

表1

实时荧光定量逆转录PCR所用引物序列"

Genes Primer
FABP6S Forward：5′-CCACCCATTCTCCTCATCCCTCTGCTC-3′
Reverse：5′-ACCAAGTGAAGTCCTGCCCATCCTG-3′
FABP6L Forward：5′-ACATGGGTGAGCCGGAAAGGAGAC-3′
Reverse：5′-CCGGAGTAGTGCTGGGACCAAGTGAAGT-3′

图1

正常肾小管细胞系和肾癌细胞系中FABP6基因mRNA的表达水平"

图2

正常肾小管细胞和肾癌细胞系中FABP6L mRNA的表达情况"

图3

正常肾小管细胞和肾癌细胞系和中FABP6蛋白的表达情况，HCT116为已报道的FABP6高表达阳性对照细胞"

图4

癌旁正常肾组织和ccRCC组织中FABP6蛋白的表达情况"

图5

FABP6 mRNA在癌旁正常肾组织和ccRCC组织中的表达情况"

图6

A498和CAKI1细胞系的过表达效率验证"

图7

A498和CAKI1细胞系的克隆形成实验"

图8

769P细胞系的敲低效率验证"

图9

769P细胞系的EdU增殖实验(×20)"

1
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ISSN 1671-167X
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