EPS8L3 promotes pancreatic cancer proliferation and metastasis by activating GSK3B.

IF 2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zun Fan, Ming Li, Yinjie Xu, Chenxing Ge, Jianfeng Gu
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引用次数: 1

Abstract

Background: We intended to investigate the role and regulatory mechanism of EPS8L3 in increase the development of pancreatic cancer (PC).

Methods: In order to analyze the relationship between EPS8L3 level and clinicopathological indicators of PC patients, qRT-PCR was used to detect the expression of EPS8L3 in tumor specimens of 40 PC patients. EPS8L3 knockdown models were then constructed in PC cell lines. Furthermore, the effect of EPS8L3 on PC cell function was analyzed by CCK-8 and Transwell assay. Dual luciferase reporter gene assay and recovery assay were used to further investigate the underlying mechanism.

Results: qRT-PCR results indicated that EPS8L3 was highly expressed in PC tissues compared with adjacent ones. At the same time, the incidence of distant metastasis was higher in PC patients with high EPS8L3 level. In vitro analysis such as CCK-8 and Transwell experimentations indicated that knockdown of EPS8L3 markedly inhibited the proliferative and metastatic ability. Bio-informatics together with luciferase report assay proposing that EPS8L3 can target GSK3B. Western Blot results revealed that knockdown of EPS8L3 markedly reduced the GSK3B expression in PC cells, and there was a positively associated between the two in PC cells. In addition, the recovery experimentation proved that EPS8L3 and GSK3B have a mutual regulation effect. Overexpression of GSK3B can reversal the prohibitive effect of EPS8L3 knockdown on the malignant development of PC cells, thereby jointly regulating the occurrence and development of PC.

Conclusions: EPS8L3 promotes the development of PC by regulating GSK3B, suggesting that EPS8L3 can be used as a biomarker for early diagnosis and treatment of PC.

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EPS8L3通过激活GSK3B促进胰腺癌的增殖和转移。
背景:我们旨在研究EPS8L3在胰腺癌(PC)发展中的作用和调控机制。方法:为分析EPS8L3水平与PC患者临床病理指标的关系,采用qRT-PCR检测40例PC患者肿瘤标本中EPS8L3的表达。然后在PC细胞系中构建EPS8L3敲低模型。通过CCK-8和Transwell实验分析EPS8L3对PC细胞功能的影响。采用双荧光素酶报告基因法和回收率法进一步探讨其作用机制。结果:qRT-PCR结果显示EPS8L3在PC组织中较邻近组织高表达。同时,EPS8L3水平较高的PC患者远处转移的发生率较高。CCK-8和Transwell实验等体外分析表明,敲低EPS8L3可显著抑制细胞的增殖和转移能力。生物信息学结合荧光素酶报告实验表明EPS8L3可以靶向GSK3B。Western Blot结果显示,敲低EPS8L3可显著降低PC细胞中GSK3B的表达,两者在PC细胞中呈正相关。此外,恢复实验证明EPS8L3和GSK3B具有相互调节作用。GSK3B过表达可逆转EPS8L3敲低对PC细胞恶性发展的抑制作用,共同调控PC的发生发展。结论:EPS8L3通过调控GSK3B促进PC的发展,提示EPS8L3可作为PC早期诊断和治疗的生物标志物。
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来源期刊
Journal of Medical Biochemistry
Journal of Medical Biochemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
3.00
自引率
12.00%
发文量
60
审稿时长
>12 weeks
期刊介绍: The JOURNAL OF MEDICAL BIOCHEMISTRY (J MED BIOCHEM) is the official journal of the Society of Medical Biochemists of Serbia with international peer-review. Papers are independently reviewed by at least two reviewers selected by the Editors as Blind Peer Reviews. The Journal of Medical Biochemistry is published quarterly. The Journal publishes original scientific and specialized articles on all aspects of clinical and medical biochemistry, molecular medicine, clinical hematology and coagulation, clinical immunology and autoimmunity, clinical microbiology, virology, clinical genomics and molecular biology, genetic epidemiology, drug measurement, evaluation of diagnostic markers, new reagents and laboratory equipment, reference materials and methods, reference values, laboratory organization, automation, quality control, clinical metrology, all related scientific disciplines where chemistry, biochemistry, molecular biology and immunochemistry deal with the study of normal and pathologic processes in human beings.
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