肺腺癌中可变剪接调控因子KHSRP调控的差异剪接基因分析

刘晓丽, 柴文君, 孙磊, 闫明霞, 潘洪玉, 孙跃喜

1.复旦大学附属肿瘤医院肿瘤研究所，复旦大学上海医学院肿瘤学系，上海 200032
2.同济大学附属同济医院急诊医学科，上海 200065

收稿日期:2023-04-15 修回日期:2023-06-27 出版日期:2023-07-30 发布日期:2023-08-10
通信作者: 孙跃喜 E-mail:sunyuexi.love@163.com
作者简介:刘晓丽（ORCID: 0009-0002-7379-8992），博士，助理研究员。
基金资助:
国家自然科学基金面上项目(81972173);国家自然科学基金面上项目(82273371)

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摘要/Abstract

摘要：

背景与目的：可变剪接在细胞增殖、生长、凋亡及分化等复杂的蛋白质功能调控中发挥着至关重要的作用，能参与包括肿瘤在内的多种疾病的发生、发展过程，目前大多数可变剪接调控因子的功能及其作用机制尚不清楚。本研究旨在探讨KH型剪接调控蛋白（KH-type splicing regulatory protein，KHSRP）在肺腺癌中的差异剪接靶基因及靶基因的表达与患者预后及免疫细胞功能的相关性。方法：通过高通量可变剪接测序，筛选KHSRP下游差异剪接靶基因。通过肿瘤免疫评估资源（Tumor IMmune Estimation Resource，TIMER）和阿拉巴马大学伯明翰分校癌症数据分析门户（the University of Alabama at Birmingham cancer data analysis portal，ULCAN）分析KHSRP下游差异剪接靶基因在肺腺癌中的表达。通过Kaplan数据库分析KHSRP下游差异剪接靶基因的表达与患者预后的相关性。通过TIMER免疫模块分析KHSRP下游差异剪接靶基因与免疫细胞功能的相关性。结果：NUMB、ADD3及LIMCH1为KHSRP的下游关键可变剪接靶基因。NUMB、ADD3及LIMCH1在肺腺癌肿瘤组织中均呈低表达，其低表达者预后不良。NUMB、ADD3及LIMCH1与免疫细胞功能呈正相关。结论：在肺腺癌中，NUMB、ADD3及LIMCH1为KHSRP的差异剪接靶基因，且NUMB、ADD3及LIMCH1低表达会导致预后不良，并且与免疫细胞功能呈正相关。

关键词: 肺腺癌, KH型剪接调控蛋白, 可变剪接, 差异剪接靶基因

Abstract:

Background and purpose: Alternative splicing plays a crucial role in the functions and regulation of complex proteins such as cell proliferation, growth, apoptosis and differentiation, and can cause the occurrence and development of various diseases, including cancer. Currently, the functions and molecular mechanisms of most alternative splicing factors are not clear. The purpose of this study was to explore the differential splicing target genes of KH-type splicing regulatory protein (KHSRP) in lung adenocarcinoma and their correlation with prognosis and immune cell function. Methods: Screening downstream differential splicing target genes of KHSRP was carried out through high-throughput variable splicing sequencing. We analyzed the expressions of KHSRP downstream differential splicing target genes in lung adenocarcinoma through cancer databases Tumor IMmune Estimation Resource (TIMER) and the University of Alabama at Birmingham cancer data analysis portal (ULCAN). We also analyzed the correlation between the expression of differential splicing target genes downstream of KHSRP and prognosis through Kaplan database. The correlation between downstream differential splicing target genes of KHSRP and immune cell function was analyzed through the TIMER immune module. Results: NUMB endocytic adaptor protein (NUMB), adducin 3 (ADD3) and LIM and calponin homology domains 1 (LIMCH1) were key downstream variable splicing target genes of KHSRP. NUMB, ADD3 and LIMCH1 were all expressed at low level in lung adenocarcinoma tumor tissue. Low expressions of NUMB, ADD3 and LIMCH1 in lung cancer leaded to poor prognosis. NUMB, ADD3 and LIMCH1 were positively correlated with immune cell function. Conclusion: In lung adenocarcinoma, NUMB, ADD3 and LIMCH1 are differential splicing target genes of KHSRP, their low expression levels indicate poor prognosis, and they are positively correlated with immune cell function.

Key words: Lung adenocarcinoma, KH-type splicing regulatory protein, Variable splicing, Differential splicing target genes

中图分类号:

R734.2

刘晓丽, 柴文君, 孙磊, 闫明霞, 潘洪玉, 孙跃喜. 肺腺癌中可变剪接调控因子KHSRP调控的差异剪接基因分析[J]. 中国癌症杂志, 2023, 33(7): 637-645.

LIU Xiaoli, CHAI Wenjun, SUN Lei, YAN Mingxia, PAN Hongyu, SUN Yuexi. Analysis of differential splicing gene by regulation of splicing regulatory protein KHSRP in lung adenocarcinoma[J]. China Oncology, 2023, 33(7): 637-645.

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链接本文: http://www.china-oncology.com/CN/10.19401/j.cnki.1007-3639.2023.07.001

http://www.china-oncology.com/CN/Y2023/V33/I7/637

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肺腺癌中可变剪接调控因子KHSRP调控的差异剪接基因分析

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