ESF1和MIPEP蛋白促进雌激素受体阳性乳腺癌的增殖，并与患者预后有关
ESF1 and MIPEP proteins promote estrogen receptor-positive breast cancer proliferation and are associated with patient prognosis
影响因子:3.30000
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
摘要
雌激素受体阳性（ER+）乳腺癌占所有乳腺癌的三分之二，其早期和晚期的复发仍威胁着患者的长期生存和生活质量。寻找候选肿瘤抗原和潜在的治疗靶标对于满足这些未满足的需求至关重要。采用了相对定量和绝对定量（ITRAQ）的同种异性标签来识别ER+乳腺癌和相应邻近正常组织之间差异表达的蛋白质（DEP）。通过生物信息学分析筛选候选DEP，并通过免疫组织化学（IHC）染色和蛋白质印迹证实其表达。进行了一系列体外实验，包括伤口愈合测定，菌落形成和细胞周期测定，以揭示所选DEP的功能。此外，进一步分析了它们的临床意义。总共发现了369个DEP（折叠变化≥2.0或≤0.66，p <0.05）。与正常组织相比，在ER+乳腺癌中下调了358种蛋白质，11种蛋白质下调。 GO和KEGG富集分析表明，DEP与RNA调节和代谢途径密切相关。 String分析发现ESF1和MIPEP是乳腺癌中的枢纽基因，其表达式增加了IHC染色和蛋白质印迹。击倒ESF1和MIPEP抑制了菌落形成并增加细胞凋亡。此外，击倒ESF1抑制了伤口愈合，但不能抑制MIPEP。此外，ESF1和MIPEP表达与患者预后呈负相关。ESF1和MIPEP的上调促进了ER+乳腺癌的扩散，这可能为开发新疗法提供新的靶标。
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.