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微小RNA-137通过靶向谷氨酰胺酶抑制恶性黑色素瘤的谷氨酰胺分解代谢和生长。

miR-137 inhibits glutamine catabolism and growth of malignant melanoma by targeting glutaminase.

作者信息

Luan Wenkang, Zhou Zhou, Zhu Yan, Xia Yun, Wang Jinlong, Xu Bin

机构信息

Department of Plastic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

Department of Neurosurgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

出版信息

Biochem Biophys Res Commun. 2018 Jan 1;495(1):46-52. doi: 10.1016/j.bbrc.2017.10.152. Epub 2017 Oct 31.

DOI:10.1016/j.bbrc.2017.10.152
PMID:29097210
Abstract

Glutamine catabolism is considered to be an important metabolic pathway for cancer cells. Glutaminase (GLS) is the important rate-limiting enzyme of glutamine catabolism. miR-137 functions as a tumor suppressor in many human malignant tumors. However, the role and molecular mechanism of miR-137 and GLS in malignant melanoma has not been reported. In this study, we showed that miR-137 was decreased in melanoma tissue, and the low miR-137 level and high GLS expression are independent risk factor in melanoma. miR-137 suppressed the proliferation and glutamine catabolism of melanoma cells. GLS is crucial for glutamine catabolism and growth of malignant melanoma. We also demonstrated that miR-137 acts as a tumor suppressor in melanoma by targeting GLS. This result elucidates a new mechanism for miR-137 in melanoma development and provides a survival indicator and potential therapeutic target for melanoma patients.

摘要

谷氨酰胺分解代谢被认为是癌细胞的一条重要代谢途径。谷氨酰胺酶(GLS)是谷氨酰胺分解代谢的重要限速酶。miR-137在许多人类恶性肿瘤中发挥肿瘤抑制作用。然而,miR-137和GLS在恶性黑色素瘤中的作用及分子机制尚未见报道。在本研究中,我们发现miR-137在黑色素瘤组织中表达降低,低水平的miR-137和高水平的GLS表达是黑色素瘤的独立危险因素。miR-137抑制黑色素瘤细胞的增殖和谷氨酰胺分解代谢。GLS对恶性黑色素瘤的谷氨酰胺分解代谢和生长至关重要。我们还证明miR-137通过靶向GLS在黑色素瘤中发挥肿瘤抑制作用。这一结果阐明了miR-137在黑色素瘤发生发展中的新机制,并为黑色素瘤患者提供了一个生存指标和潜在的治疗靶点。

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