Chen Xueru, Xiang Zijin, Li Dangchi, Zhu Xiuting, Peng Xiangdong
Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
Jiangxi University of Technology High School, Nanchang, Jiangxi 330029, P.R. China.
Exp Ther Med. 2021 Feb;21(2):175. doi: 10.3892/etm.2020.9606. Epub 2020 Dec 28.
Molecular-targeted therapy has had a significant impact on glioma. Notably, actin-like 6A (ACTL6A) has been indicated to be essential for embryonic development and tumor progression. However, the role of ACTL6A in glioma remains unclear. The present study aimed to investigate the effects of ACTL6A on glioma cell migration and sensitivity to temozolomide (TMZ). The expression levels of ACTL6A were analyzed in patients with glioma, and survival curves were created using data from The Cancer Genome Atlas. U251 and T98G cells were transfected with short hairpin (sh)RNA for use in loss-of-function experiments to investigate the biological function and molecular mechanisms of ACTL6A. Furthermore, an MTT assay was used to assess the effect of ACTL6A on the sensitivity of glioma cells to TMZ. The results demonstrated that ACTL6A was expressed at higher levels in glioma tissues compared with normal brain tissues. Furthermore, high expression of ACTL6A was associated with a poor prognosis. The knockdown of ACTL6A significantly inhibited the migration phenotype in glioma cells and significantly decreased the levels of phosphorylated AKT in glioma cells. The AKT signaling activator SC79 partly attenuated the inhibitory effects of ACTL6A shRNA on glioma cell migration. Additionally, the knockdown of ACTL6A enhanced the sensitivity of glioma cells to TMZ. In conclusion, these results suggest that ACTL6A knockdown inhibited the migration of human glioma cells, at least in part through inactivation of the AKT signaling pathway, and increased the sensitivity of glioma cells to TMZ. Therefore, ACTL6A may be a potential therapeutic target for glioma.
分子靶向治疗对胶质瘤产生了重大影响。值得注意的是，肌动蛋白样6A（ACTL6A）已被表明对胚胎发育和肿瘤进展至关重要。然而，ACTL6A在胶质瘤中的作用仍不清楚。本研究旨在探讨ACTL6A对胶质瘤细胞迁移和对替莫唑胺（TMZ）敏感性的影响。分析了胶质瘤患者中ACTL6A的表达水平，并使用来自癌症基因组图谱的数据绘制了生存曲线。用短发夹（sh）RNA转染U251和T98G细胞，用于功能丧失实验，以研究ACTL6A的生物学功能和分子机制。此外，采用MTT法评估ACTL6A对胶质瘤细胞对TMZ敏感性的影响。结果表明，与正常脑组织相比，ACTL6A在胶质瘤组织中的表达水平更高。此外，ACTL6A的高表达与预后不良相关。敲低ACTL6A可显著抑制胶质瘤细胞的迁移表型，并显著降低胶质瘤细胞中磷酸化AKT的水平。AKT信号激活剂SC79部分减弱了ACTL6A shRNA对胶质瘤细胞迁移的抑制作用。此外，敲低ACTL6A可增强胶质瘤细胞对TMZ的敏感性。总之，这些结果表明，敲低ACTL6A至少部分通过AKT信号通路的失活抑制了人胶质瘤细胞的迁移，并增加了胶质瘤细胞对TMZ的敏感性。因此，ACTL6A可能是胶质瘤的一个潜在治疗靶点。
