ZFP36L1 Promotes Gastric Cancer Progression via Regulating JNK and p38 MAPK Signaling Pathways.

IF 2.5 4区 医学 Q3 ONCOLOGY
Kang Ding, Fengping Zhang, Gaoxiu Qi, Meng Lin Lin, Min Chen, Yanchun Chen, Jie Zheng, Fenghua Zhou
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引用次数: 2

Abstract

Background: The RNA-binding protein Zinc Finger Protein 36 like 1(ZFP36L1) plays an important role in regulating the AU-rich elements (AREs) in the 3' untranslated region (3' UTR) of mRNAs, indicating a potential link between its expression and cancers. However, the role and mechanism of ZFP36L1 in gastric cancer (GC) are unclear.

Objectives: This study aimed to explore the role and mechanism of ZFP36L1 in gastric cancer.

Materials and methods: GC tissue samples and matched normal gastric tissues were collected, and the ZFP36L1 expression in these samples was evaluated by immunohistochemistry analysis. GC cells with different differentiation were selected for in vitro experiments. The ZFP36L1 expression in GC cells was examined by quantitative real-time polymerase chain reaction (qRTPCR) and Western blot analysis. The viability and invasiveness of GC cells were assayed by 5- Ethynyl-2-deoxyuridine (EdU) and Transwell assays, respectively. Western blot assay was used to detect the expression of epithelial-to-mesenchymal transition (EMT) related proteins and proteins of the c-Jun N-terminal kinase (JNK) and p38 Mitogen-Activated Protein Kinase (MAPK) signaling pathways.

Results: ZFP36L1 is overexpressed in GC tissues. Patients with high ZFP36L1 expression have a poor prognosis. Moreover, ZFP36L1 is overexpressed in the cell lines with a high degree of malignancy. ZFP36L1 increases cell proliferation, invasion, and migration in vitro. Furthermore, ZFP36L1 induces EMT. The JNK inhibitor and p38 inhibitor alone or in combination affect the biological function of GC cells. Furthermore, ZFP36L1 promotes GC progression by inhibiting JNK and p38 MAPK signaling pathways.

Conclusion: RNA-binding protein ZFP36L1 exerts a role in the occurrence of gastric cancer by the regulation of the JNK and p38 MAPK signaling pathways. The combination of inhibitors of the JNK and p38 MAPK signaling pathways could be a novel treatment strategy for gastric cancer.

ZFP36L1通过调控JNK和p38 MAPK信号通路促进胃癌进展。
背景:rna结合蛋白锌指蛋白36样1(ZFP36L1)在调控mrna 3'非翻译区(3' UTR)的富au元件(AREs)中发挥重要作用,提示其表达与癌症之间存在潜在联系。然而,ZFP36L1在胃癌(GC)中的作用和机制尚不清楚。目的:探讨ZFP36L1在胃癌中的作用及机制。材料和方法:收集GC组织样本和匹配的正常胃组织,通过免疫组织化学分析评估ZFP36L1在这些样本中的表达。选择不同分化的GC细胞进行体外实验。采用定量实时聚合酶链反应(qRTPCR)和Western blot检测GC细胞中ZFP36L1的表达。采用5-乙基-2-脱氧尿苷(EdU)法和Transwell法测定GC细胞的活力和侵袭性。Western blot检测上皮-间质转化(EMT)相关蛋白、c-Jun n-末端激酶(JNK)和p38丝裂原活化蛋白激酶(MAPK)信号通路蛋白的表达。结果:ZFP36L1在GC组织中过表达。ZFP36L1高表达的患者预后较差。此外,ZFP36L1在恶性程度高的细胞系中过表达。ZFP36L1增加体外细胞增殖、侵袭和迁移。此外,ZFP36L1诱导EMT。JNK抑制剂和p38抑制剂单独或联合作用影响GC细胞的生物学功能。此外,ZFP36L1通过抑制JNK和p38 MAPK信号通路促进GC进展。结论:rna结合蛋白ZFP36L1通过调控JNK和p38 MAPK信号通路参与胃癌的发生。联合抑制JNK和p38 MAPK信号通路可能是一种新的胃癌治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.50
自引率
7.10%
发文量
55
审稿时长
3 months
期刊介绍: Aims & Scope Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.
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