Peng Yong, Zhang Mingming, Jiang Zhongzhong, Jiang Yugang
Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China,
Onco Targets Ther. 2019 Jan 3;12:397-404. doi: 10.2147/OTT.S188101. eCollection 2019.
Tripartite motif-containing protein 28 (TRIM28) is a transcriptional corepressor involved in the regulation of several cancers, including glioma. It has been reported that TRIM28 takes part in the process of autophagy. However, its effect on the autophagy and cell proliferation in gliomas has not been elucidated. Here, we report a novel tumor cell proliferation mechanism in which TRIM28-regulated autophagy promotes glioma tumor cell proliferation.
We analyzed the expressions of TRIM28 and LC3 in different WHO grades of gliomas by IHC assays. We then knocked down and overexpressed TRIM28 or knocked down ATG5 in U251 cells and confirmed its roles in autophagy and cell proliferation via cell counting, immunofluorescence, and Western blot.
The results showed that TRIM28 and autophagy levels were significantly increased with the progression of tumor grade in glioma. TRIM28 promoted glioblastoma cell proliferation. Knockdown of TRIM28 inhibited autophagy in glioblastoma cells. Meanwhile, TRIM28 promoted glioblastoma cell proliferation by modulating TRIM28.
These data demonstrated that TRIM28 activates autophagy and increases cell proliferation in glioma.
含三联基序蛋白28（TRIM28）是一种转录共抑制因子，参与包括胶质瘤在内的多种癌症的调控。据报道，TRIM28参与自噬过程。然而，其对胶质瘤自噬和细胞增殖的影响尚未阐明。在此，我们报道一种新的肿瘤细胞增殖机制，即TRIM28调节的自噬促进胶质瘤肿瘤细胞增殖。
我们通过免疫组化分析不同世界卫生组织（WHO）分级的胶质瘤中TRIM28和LC3的表达。然后，我们在U251细胞中敲低和过表达TRIM28或敲低自噬相关基因5（ATG5），并通过细胞计数、免疫荧光和蛋白质印迹法确认其在自噬和细胞增殖中的作用。
结果显示，在胶质瘤中，TRIM28和自噬水平随肿瘤分级进展显著升高。TRIM28促进胶质母细胞瘤细胞增殖。敲低TRIM28可抑制胶质母细胞瘤细胞的自噬。同时，TRIM28通过调节自噬促进胶质母细胞瘤细胞增殖。
这些数据表明，TRIM28激活自噬并增加胶质瘤细胞增殖。
