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通过RNA干扰敲低天冬酰胺合成酶可抑制人黑素瘤细胞和表皮样癌细胞的生长。

Knockdown of asparagine synthetase by RNAi suppresses cell growth in human melanoma cells and epidermoid carcinoma cells.

作者信息

Li Hui, Zhou Fusheng, Du Wenhui, Dou Jinfa, Xu Yu, Gao Wanwan, Chen Gang, Zuo Xianbo, Sun Liangdan, Zhang Xuejun, Yang Sen

机构信息

Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.

出版信息

Biotechnol Appl Biochem. 2016 May;63(3):328-33. doi: 10.1002/bab.1383. Epub 2015 Jul 6.

Abstract

Melanoma, the most aggressive form of skin cancer, causes more than 40,000 deaths each year worldwide. And epidermoid carcinoma is another major form of skin cancer, which could be studied together with melanoma in several aspects. Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine, and its expression is associated with the chemotherapy resistance and prognosis in several human cancers. The present study aims to explore the potential role of ASNS in melanoma cells A375 and human epidermoid carcinoma cell line A431. We applied a lentivirus-mediated RNA interference (RNAi) system to study its function in cell growth of both cells. The results revealed that inhibition of ASNS expression by RNAi significantly suppressed the growth of melanoma cells and epidermoid carcinoma cells, and induced a G0/G1 cell cycle arrest in melanoma cells. Knockdown of ASNS in A375 cells remarkably downregulated the expression levels of CDK4, CDK6, and Cyclin D1, and upregulated the expression of p21. Therefore, our study provides evidence that ASNS may represent a potential therapeutic target for the treatment of melanoma.

摘要

黑色素瘤是最具侵袭性的皮肤癌形式,每年在全球导致超过40000人死亡。而表皮样癌是皮肤癌的另一种主要形式,在多个方面可与黑色素瘤一起进行研究。天冬酰胺合成酶(ASNS)基因编码一种催化天冬氨酸在谷氨酰胺和ATP依赖下转化成天冬酰胺的酶,其表达与多种人类癌症的化疗耐药性和预后相关。本研究旨在探讨ASNS在黑色素瘤细胞A375和人表皮样癌细胞系A431中的潜在作用。我们应用慢病毒介导的RNA干扰(RNAi)系统来研究其在两种细胞生长中的功能。结果显示,RNAi抑制ASNS表达可显著抑制黑色素瘤细胞和表皮样癌细胞的生长,并诱导黑色素瘤细胞发生G0/G1期细胞周期阻滞。敲低A375细胞中的ASNS可显著下调CDK4、CDK6和细胞周期蛋白D1的表达水平,并上调p21的表达。因此,我们的研究提供了证据表明ASNS可能是治疗黑色素瘤的一个潜在治疗靶点。

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