酰基辅酶 A 中链合成酶 3（ACSM3）受胰岛素样生长因子 2 mRNA 结合蛋白 3（IGF2BP3）调控，抑制乳腺浸润性癌的增殖、迁移和干细胞特性。

Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Is Regulated by Insulin Like Growth Factor 2 mRNA Binding Protein 3 (IGF2BP3) and Inhibits Proliferation, Motility and Stem Cell Properties of Breast Invasive Carcinoma.

机构信息

Department of Breast Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China

Department of Breast Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.

出版信息

Ann Clin Lab Sci. 2023 Jul;53(4):539-547.

PMID:37625834

Abstract

OBJECTIVE

Breast invasive carcinoma (BRCA) has a high degree of malignancy, is prone to lymph node metastasis, and has a poor prognosis. This study aimed to explore the role of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) in BRCA, which was found down-regulated in liver cancer and malignant melanoma.

METHODS

The expression level of ACSM3 in patients with BRCA and its correlation with the overall survival rate was analyzed. The impacts of ACSM3 on BRCA cell proliferation, motility and stem cell properties were then evaluated. The association between insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) and ACSM3 was verified, the influences of IGF2BP3 on the regulation of ACSM3 on cells were determined.

RESULTS

Down-regulated ACSM3 level was associated with poor overall survival. ACSM3 overexpression weakened BRCA cell proliferation, motility and stem cell properties. Importantly, IGF2BP3 destabilized ACSM3 and downregulated its expression level. IGF2BP3 overexpression reversed the impacts of ACSM3 overexpression on cells, indicating that ACSM3 was regulated by IGF2BP3 in BRCA cells.

CONCLUSION

We found that ACSM3 was regulated by IGF2BP3 and attenuated BRCA proliferation, invasion and stem cell properties. The role of ACSM3 in BRCA was first revealed, which provides a novel target for treatment.

摘要

目的

乳腺浸润性癌（BRCA）恶性程度高，易发生淋巴结转移，预后不良。本研究旨在探讨酰基辅酶 A 中链合成酶 3（ACSM3）在肝癌和恶性黑色素瘤中下调的 BRCA 中的作用。

方法

分析 ACSM3 在 BRCA 患者中的表达水平及其与总生存率的相关性。然后评估 ACSM3 对 BRCA 细胞增殖、运动性和干细胞特性的影响。验证胰岛素样生长因子 2 mRNA 结合蛋白 3（IGF2BP3）与 ACSM3 的关联，确定 IGF2BP3 对 ACSM3 调节细胞的影响。

结果

下调的 ACSM3 水平与总生存率不良相关。ACSM3 过表达减弱了 BRCA 细胞的增殖、运动性和干细胞特性。重要的是，IGF2BP3 使 ACSM3 不稳定并下调其表达水平。IGF2BP3 过表达逆转了 ACSM3 过表达对细胞的影响，表明 IGF2BP3 在 BRCA 细胞中调节 ACSM3。