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跨膜蛋白106a是人类肾癌中的一种新型肿瘤抑制因子。

TMEM106a is a Novel Tumor Suppressor in Human Renal Cancer.

作者信息

Wu Chenglong, Xu Juan, Wang Han, Zhang Jinghua, Zhong Jianhua, Zou Xiaowen, Chen Yan, Yang Gang, Zhong Yuantang, Lai Daihuan, Li Xuyi, Tang Aifa

机构信息

Shenzhen Second People's Hospital, Guangzhou Medical University, Shenzhen, China.

Department of Urinary Surgery, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.

出版信息

Kidney Blood Press Res. 2017;42(5):853-864. doi: 10.1159/000484495. Epub 2017 Oct 31.

Abstract

BACKGROUND/AIMS: In recent years the diagnosis and management of renal cancer has changed greatly, although the mechanism is still elusive. TMEM106a is a conserved type II transmembrane protein which is a key factor to regulate macrophage activation. Its inactivation in gastric cancer is frequently observed to be associated with poor prognosis. The role of TMEM106a in renal cancer remained unclear.

METHODS

TMEM106a expression profiling was performed in a panel of renal cancer cell lines and primary renal tissue cells. Then TMEM106a was overexpressed by a viral system in a renal cancer cell line with low level of TMEM106a. This stable cell line was assessed in multiple cell growth and migration assays. The results from TMEM106a overexpressing cell line were then confirmed with primary renal cells by siRNA knockdown of TMEM106a.

RESULTS

TMEM106a expression level was reduced in renal cancer cells compared to normal primary renal cells. Restoration of TMEM106a expression in TMEM106a-low renal cancer cells resulted in attenuated proliferation, reduced cell migration and enhanced caspase 3 dependent apoptosis compared to control cells. TMEM106a knockdown in primary renal cells led to increased colony formation compared to the control cells with scrambled siRNA transfection.

CONCLUSION

TMEM106a is a novel tumor suppressor in renal cancer.

摘要

背景/目的:近年来,肾癌的诊断和治疗发生了很大变化,但其机制仍不清楚。跨膜蛋白106a(TMEM106a)是一种保守的II型跨膜蛋白,是调节巨噬细胞活化的关键因子。在胃癌中经常观察到其失活与预后不良有关。TMEM106a在肾癌中的作用仍不清楚。

方法

在一组肾癌细胞系和原发性肾组织细胞中进行TMEM106a表达谱分析。然后,通过病毒系统在TMEM106a水平较低的肾癌细胞系中过表达TMEM106a。在多种细胞生长和迁移试验中评估这种稳定的细胞系。然后通过小干扰RNA(siRNA)敲低原发性肾细胞中的TMEM106a,用原发性肾细胞证实过表达TMEM106a细胞系的结果。

结果

与正常原发性肾细胞相比,肾癌细胞中TMEM106a表达水平降低。与对照细胞相比,在TMEM106a低表达的肾癌细胞中恢复TMEM106a表达导致增殖减弱、细胞迁移减少和半胱天冬酶3依赖性凋亡增强。与转染乱序siRNA的对照细胞相比,原发性肾细胞中TMEM106a敲低导致集落形成增加。

结论

TMEM106a是肾癌中的一种新型肿瘤抑制因子。

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