ESF1和MIPEP蛋白促进雌激素受体阳性乳腺癌增殖并与患者预后相关

ESF1 and MIPEP proteins promote estrogen receptor-positive breast cancer proliferation and are associated with patient prognosis

Clinical Proteomics

影响因子:3.3

分区:医学3区 / 生化研究方法2区

发表日期:2024 Jul 15

作者: Qing Yu, Chunhua Qu, Jinliang Liang, Peiqi Chen, Kaiying Zhang, Yanji Zhang, Yuening Zhang, Zherui Li, Shaojun Liu, Zhaoshou Yang, Hongyan Sun, Anli Yang

DOI: 10.1186/s12014-024-09502-8

摘要

雌激素受体阳性（ER+）乳腺癌占所有乳腺癌的三分之二，其早期和晚期复发仍威胁患者的长期生存和生活质量。寻找候选肿瘤抗原和潜在治疗靶点对于满足这一未被满足的需求至关重要。采用等重比标签相对与绝对定量（iTRAQ）蛋白组学分析，鉴定出ER+乳腺癌与对应正常组织之间差异表达的蛋白（DEPs）。通过生物信息学分析筛选候选DEPs，并用免疫组化（IHC）染色和Western blot验证其表达。进行一系列体外实验，包括伤口愈合、克隆形成和细胞周期检测，以揭示所选DEPs的功能，并进一步分析其临床意义。发现共有369个DEPs（折叠变化≥2.0或≤0.66，P<0.05），其中358个蛋白在ER+乳腺癌中表达上调，11个表达下调。GO和KEGG富集分析显示，DEPs主要与RNA调控和代谢通路相关。STRING分析指出，ESF1和MIPEP是乳腺癌的核心基因，其表达上调在免疫组化和Western blot中得到验证。敲低ESF1和MIPEP后，抑制了克隆形成并增加细胞凋亡，且敲低ESF1还抑制了伤口愈合，MIPEP则无显著影响。此外，ESF1和MIPEP的高表达与患者预后呈负相关。综上所述，ESF1和MIPEP的上调促进ER+乳腺癌的增殖，可能为新疗法的开发提供新的靶点。

Abstract

Estrogen receptor-positive (ER+) breast cancer accounts for two-thirds of all breast cancers, and its early and late recurrences still threaten patients' long-term survival and quality of life. Finding candidate tumor antigens and potential therapeutic targets is critical to addressing these unmet needs.The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to identify the differentially expressed proteins (DEPs) between ER + breast cancer and corresponding adjacent normal tissue. Candidate DEPs were screened by bioinformatic analyses, and their expression was confirmed by immunohistochemical (IHC) staining and western blot. A series of in vitro experiments, including wound healing assay, colony formation, and cell cycle assay, were performed to reveal the functions of selected DEPs. Additionally, their clinical significances were further analyzed.A total of 369 DEPs (fold change ≥ 2.0 or ≤ 0.66, P < 0.05) were discovered. Compared with normal tissue, 358 proteins were up-regulated and 11 proteins were down-regulated in ER + breast cancer. GO and KEGG enrichment analysis showed that DEPs were closely associated with RNA regulation and metabolic pathways. STRING analysis found ESF1 and MIPEP were the hub genes in breast cancer, whose increased expressions were verified by the IHC staining and western blot. Knocking down ESF1 and MIPEP inhibited colony formation and increased cell apoptosis. Besides, knocking down ESF1 inhibited wound healing but not MIPEP. In addition, ESF1 and MIPEP expression were negatively associated with patient prognosis.The upregulation of ESF1 and MIPEP promoted ER + breast cancer proliferation, which might provide novel targets for the development of new therapies.