RFC5与STAT3形成转录复合物通过c-Myc驱动非小细胞肺癌进展

RFC5 and STAT3 form a transcriptional complex to drive NSCLC progression via c-Myc.

期刊: iScience
PMID: 42662404
原文: PubMed ↗
发布日期: 2026-08-28

作者

Jinhua Yan — Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Tao Yi — Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.
Wentao Tian — Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410028, China.
Jinzheng Wu — Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Rongji Yu — Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.
Shumiao Zhang — Beijing Milu Ecological Research Center, Beijing 100076, China.
Zekun Cheng — Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Xiaotang Di — Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.
Hao Jiang — Department of Biomedical Informatics, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.
Doudou Wen — Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.
Shubing Zhang — Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.

作者单位

Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410028, China.
Beijing Milu Ecological Research Center, Beijing 100076, China.
Department of Biomedical Informatics, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.

摘要

中文

非小细胞肺癌（NSCLC）是全球癌症死亡的主要原因，常以晚期诊断和治疗抵抗为特征，影响患者预后。本研究确定复制因子C亚基5（RFC5）是NSCLC进展中的关键致癌蛋白。多阶段NSCLC组织的单细胞转录组分析显示，RFC5是高增殖和迁移性肿瘤亚群最特异的标志物。RFC5促进NSCLC恶性表型。机制上，RFC5与STAT3相互作用并激活STAT3，作为共转录激活因子上调癌基因c-Myc的表达。此外，GATA3是RFC5的上游负调控因子。总之，本研究揭示RFC5发挥共转录激活功能，受GATA3负调控，通过激活STAT3-c-Myc信号通路促进NSCLC进展。因此，RFC5是NSCLC有前景的预后生物标志物和治疗靶点。

English

Non-small cell lung cancer (NSCLC), a leading cause of cancer death worldwide, is often characterized by late diagnosis and treatment resistance, which adversely affect patient prognosis. This study identified replication factor C subunit 5 (RFC5) as a critical oncoprotein in NSCLC progression. Single-cell transcriptomic analysis of multi-stage NSCLC tissues revealed RFC5 as the most specific marker for a highly proliferative and migratory tumor subpopulation. RFC5 promoted NSCLC malignant phenotypes. Mechanistically, RFC5 interacted with and activated STAT3, functioning as a co-transcriptional activator to upregulate the expression of the oncogene c-Myc. Furthermore, GATA3 acts as an upstream negative regulator of RFC5. Collectively, this study revealed that RFC5 exerted a co-transcriptional activation function, which was negatively regulated by GATA3, to promote NSCLC progression by activating the STAT3-c-Myc signaling pathway. Thus, RFC5 represented a promising prognostic biomarker and therapeutic target for NSCLC.

分类与指标

研究类型: 基础研究
病种: 肺癌
JCR 分区: Q1
影响因子: 4.5
新锐分区: 3区