Role of TPD52 in Endometrial Cancer: Impact on EMT and the PI3K/AKT and ERK/MAPK Signaling.

IF 2.5 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lu Miao, Buze Chen, Linlin Li, Benhong Ma, Guochen Yang, Li Jing
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引用次数: 0

Abstract

Introduction: Endometrial carcinoma (EC) incidence and mortality continue to rise, and reliable therapeutic targets remain scarce. We aimed to define the oncogenic role and mechanism of tumor protein D52 (TPD52) in EC, focusing on epithelial-mesenchymal transition (EMT) and the PI3K/AKT and ERK/MAPK signaling pathways.

Methods: In this study, we assessed the expression levels of TPD52 in EC tissues and benign endometrial tissues using immunohistochemistry. To further investigate the role of TPD52, we performed experiments both in vitro and in vivo. We transfected siRNA and overexpression (OE) plasmids into Ishikawa and HEC-1-A cell lines to knock down (KD) or overexpress TPD52, respectively. We observed the effects of TPD52 knockdown on tumor growth and EMT through in vitro experiments.

Results: TPD52 was significantly upregulated in EC tissues compared with those of benign endometrial tissues. Silencing TPD52 significantly inhibited cell proliferation, migration, and invasion, whereas TPD52 overexpression produced the opposite effects. TPD52 facilitates epithelial-mesenchymal transition (EMT). Moreover, TPD52 stimulates the PI3K/AKT and ERK/MAPK signaling pathways.

Discussion: These data position TPD52 as a bona fide EC oncoprotein that drives EMT via dual PI3K/AKT-ERK/MAPK signaling. Limitations include the modest patient cohort and the lack of clinical-pathological correlation analyses.

Conclusion: TPD52 promotes EC progression through EMT and PI3K/AKT and ERK/MAPK activation, offering a promising therapeutic target whose clinical utility warrants further investigation.

TPD52在子宫内膜癌中的作用:对EMT和PI3K/AKT和ERK/MAPK信号的影响
引言:子宫内膜癌(EC)的发病率和死亡率持续上升,可靠的治疗靶点仍然缺乏。我们的目的是确定肿瘤蛋白D52 (TPD52)在EC中的致癌作用和机制,重点关注上皮-间质转化(EMT)和PI3K/AKT和ERK/MAPK信号通路。方法:采用免疫组化方法检测TPD52在EC组织和良性子宫内膜组织中的表达水平。为了进一步研究TPD52的作用,我们进行了体外和体内实验。我们将siRNA和过表达(OE)质粒分别转染到Ishikawa和HEC-1-A细胞系中,分别下调(KD)或过表达TPD52。我们通过体外实验观察TPD52基因敲低对肿瘤生长和EMT的影响。结果:与良性子宫内膜组织相比,EC组织中TPD52表达明显上调。沉默TPD52显著抑制细胞增殖、迁移和侵袭,而过表达TPD52则产生相反的效果。TPD52促进上皮-间质转化(EMT)。此外,TPD52刺激PI3K/AKT和ERK/MAPK信号通路。讨论:这些数据表明TPD52是一种真正的EC癌蛋白,通过PI3K/AKT-ERK/MAPK双信号通路驱动EMT。局限性包括适度的患者队列和缺乏临床病理相关性分析。结论:TPD52通过EMT和PI3K/AKT和ERK/MAPK激活促进EC进展,是一个有前景的治疗靶点,其临床应用有待进一步研究。
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来源期刊
Protein and Peptide Letters
Protein and Peptide Letters 生物-生化与分子生物学
CiteScore
2.90
自引率
0.00%
发文量
98
审稿时长
2 months
期刊介绍: Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis
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