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高尔基膜整合蛋白 4 可调控人类头颈部癌细胞的增殖、凋亡和细胞周期。

Golgi integral membrane protein 4 manipulates cellular proliferation, apoptosis, and cell cycle in human head and neck cancer.

机构信息

Inner Mongolia Medical University Affiliated Hospital, Hohhot, Inner Mongolia, People's Republic of China.

Inner Mongolia Medical University Affiliated Hospital, Hohhot, Inner Mongolia, People's Republic of China

出版信息

Biosci Rep. 2018 Aug 31;38(4). doi: 10.1042/BSR20180454.

Abstract

The incidence of global head and neck cancer has increased markedly in the last 10 years, and its prognosis is poor, which seriously endangers people's life and health. At present, there are few studies on its pathogenesis. Golgi integral membrane protein 4 (GOLIM4) is a major member of the Golgi apparatus transporter complex, and its role in tumor is unclear. The present study found that GOLIM4 was the key target protein downstream of stromal interaction molecule 1 (STIM1), which can inhibit the proliferation of head and neck cancer cells FaDu (human pharyngeal squamous carcinoma cell) and Tca-8113 (human tongue squamous carcinoma cell) with knockdown of GOLIM4 by lentivirus. And the decreased expression of GOLIM4 induced cellular apoptosis. Further experiments revealed that FaDu cell cycle progression was changed after GOLIM4 silence, G phase arrest and the number of G/M cells decreased significantly. It was also found that the cells in S-phase decreased markedly after GOLIM4 was knocked down compared with the control group by 5-bromo-2'-deoxyuridine (BrdU) incorporation experiment. In conclusion, we found that GOLIM4, as the target gene downstream of STIM1, inhibited the proliferation of head and neck cancer, promoted apoptosis, and regulated cell cycle progression, and GOLIM4 is a novel oncogene in head and neck cancer and might help in developing promising targetted therapies for head and neck cancer patients.

摘要

在过去的 10 年中,全球头颈部癌症的发病率显著增加,其预后较差,严重威胁着人们的生命和健康。目前,关于其发病机制的研究较少。高尔基整膜蛋白 4(GOLIM4)是高尔基器转运复合物的主要成员,其在肿瘤中的作用尚不清楚。本研究发现,GOLIM4 是基质相互作用分子 1(STIM1)下游的关键靶蛋白,通过慢病毒敲低 GOLIM4 可以抑制头颈部癌细胞 FaDu(人咽鳞癌细胞)和 Tca-8113(人舌鳞癌细胞)的增殖。并且 GOLIM4 表达下调诱导细胞凋亡。进一步的实验表明,沉默 GOLIM4 后 FaDu 细胞周期进程发生改变,G 期阻滞,G/M 期细胞数明显减少。通过 BrdU 掺入实验还发现,与对照组相比,GOLIM4 敲低后 S 期细胞明显减少。综上所述,我们发现 GOLIM4 作为 STIM1 的下游靶基因,抑制头颈部癌细胞的增殖,促进细胞凋亡,调节细胞周期进程,GOLIM4 是头颈部癌症的一种新型癌基因,可能有助于为头颈部癌症患者开发有前途的靶向治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/827c/6117616/5cd015806754/bsr-38-bsr20180454-g1.jpg

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