锌指蛋白36样蛋白1通过调节JNK和p38丝裂原活化蛋白激酶信号通路促进胃癌进展。

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

作者信息

Ding Kang, Zhang Fengping, Qi Gaoxiu, Lin Meng, Chen Min, Chen Yanchun, Zheng Jie, Zhou Fenghua

机构信息

Department of Pathology, Weifang Medical University, Weifang, Shandong, P.R. China.

Department of Pathology, Affiliated hospital, Weifang Medical University, Weifang, Shandong, PR China.

出版信息

Recent Pat Anticancer Drug Discov. 2023;18(1):80-91. doi: 10.2174/1574892817666220524102403.

DOI:10.2174/1574892817666220524102403

PMID:35611776

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.

摘要

背景

RNA结合蛋白锌指蛋白36样蛋白1（ZFP36L1）在调节mRNA 3'非翻译区（3'UTR）富含AU元件（AREs）中起重要作用，提示其表达与癌症之间可能存在联系。然而，ZFP36L1在胃癌（GC）中的作用和机制尚不清楚。

目的

本研究旨在探讨ZFP36L1在胃癌中的作用和机制。

材料与方法

收集GC组织样本及配对的正常胃组织，通过免疫组化分析评估这些样本中ZFP36L1的表达。选择不同分化程度的GC细胞进行体外实验。通过定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹分析检测GC细胞中ZFP36L1的表达。分别采用5-乙炔基-2'-脱氧尿苷（EdU）和Transwell实验检测GC细胞的活力和侵袭能力。蛋白质免疫印迹分析用于检测上皮-间质转化（EMT）相关蛋白以及c-Jun氨基末端激酶（JNK）和p38丝裂原活化蛋白激酶（MAPK）信号通路相关蛋白的表达。

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在体外可增加细胞增殖、侵袭和迁移能力。此外，ZFP36L1诱导EMT。单独或联合使用JNK抑制剂和p38抑制剂可影响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。