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Inhibition of carnitine palmitoyl transferase 1A-induced fatty acid oxidation suppresses cell progression in gastric cancer
Archives of Biochemistry and Biophysics ( IF 3.8 ) Pub Date : 2020-11-04 , DOI: 10.1016/j.abb.2020.108664
Liqiang Wang , Changfeng Li , Yumei Song , ZhenKun Yan

Background

Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyl transferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified clear.

Methods

To determine the expression of CPT1A in human GC tissues and cells and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth and invasion were evaluated by CPT1A knockdown/overexpression of GC cells in vitro.

Results

Marked upregulation of CPT1A protein expression was observed in GC cells and tissues, which was associated with grade, pathological stage, lymph node metastasis and poor prognosis in patients with GC. CPT1A overexpression also promoted the proliferation, invasion, EMT process of GC cells. In addition, CPT1A upregulation activated GC cell fatty acid oxidation (FAO) via increasing NADP+/NADPH ratio, whereas inhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration.

Conclusion

Our results examine that CPT1A-mediated FAO activation increases GC cell proliferation and migration, supporting that CPT1A is a useful prognostic biomarker and an attractive focus for GC.



中文翻译:

肉碱棕榈酰转移酶1A诱导的脂肪酸氧化抑制抑制胃癌的细胞进程

背景

胃癌(GC)的转移率很高,导致死亡。据报道,肉碱棕榈酰转移酶1a(CPT1A)在各种类型的癌症进展中起关键作用,这是抗癌治疗中的一个有吸引力的焦点。但是,尚不清楚CPT1A参与GC的潜在分子机制。

方法

确定CPT1A在人GC组织和细胞中的表达,并说明其是否与GC患者的临床病理特征和预后相关。其作用和潜在机制在调节肿瘤生长和侵袭通过CPT1A评价敲低GC细胞/过表达在体外

结果

在GC细胞和组织中观察到CPT1A蛋白表达的明显上调,这与GC患者的分级,病理分期,淋巴结转移和不良预后有关。CPT1A的过表达也促进了GC细胞的增殖,侵袭和EMT过程。此外,CPT1A上调通过增加NADP + / NADPH比值来激活GC细胞脂肪酸氧化(FAO),而抑制FAO则取消了CPT1A对GC细胞增殖和迁移的影响。

结论

我们的结果检查了CPT1A介导的FAO活化能增加GC细胞的增殖和迁移,支持CPT1A是有用的预后生物标志物,并且是GC的有吸引力的焦点。

更新日期:2020-11-16
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