Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
The Third Department, Jinan Infectious Disease Hospital, Jinan, Shandong 250021, P.R. China.
Oncol Rep. 2018 Feb;39(2):795-801. doi: 10.3892/or.2017.6117. Epub 2017 Nov 28.
Triple functional domain protein (Trio) is an evolutionarily conserved protein with guanine nucleotide exchange factors that regulate different physiological processes in some types of cancer. However, the expression and function of Trio in cervical cancer are still unknown. The purpose of this study was to detect the expression of Trio in cervical cancer tissues and to evaluate its clinical value. Furthermore, the effects of the Trio on the migration and invasion of cervical cancer cells and its mechanism were investigated in vitro. The results of the present study revealed that Trio expression levels were significantly higher in most of the clinical cervical cancer samples than in adjacent tissues. The clinicopathological significance of Trio expression was also analyzed, and the results revealed that high expression levels in cervical cancer were correlated with lymph node metastasis (P=0.005). The CRISPR/Cas9 system was used to knockdown the endogenous Trio. The inhibition of Trio significantly decreased the migration and invasion abilities of cervical cancer cells. Meanwhile, levels of RhoA/ROCK signaling factors (RhoA, Rock, and p-LIMK), which contributed to cell migration and invasion, were decreased along with the inhibition of Trio. Therefore, Trio may regulate the migration and invasion of cervical cancer through the RhoA/ROCK signaling pathway.
三重功能域蛋白（Trio）是一种进化上保守的蛋白，具有鸟嘌呤核苷酸交换因子，可调节某些类型癌症中的不同生理过程。然而，Trio 在宫颈癌中的表达和功能尚不清楚。本研究旨在检测 Trio 在宫颈癌组织中的表达，并评估其临床价值。此外，还在体外研究了 Trio 对宫颈癌细胞迁移和侵袭的影响及其机制。本研究结果表明，Trio 的表达水平在大多数临床宫颈癌样本中明显高于相邻组织。还分析了 Trio 表达的临床病理意义，结果表明宫颈癌中高表达与淋巴结转移相关（P=0.005）。使用 CRISPR/Cas9 系统敲低内源性 Trio。抑制 Trio 显著降低了宫颈癌细胞的迁移和侵袭能力。同时，促进细胞迁移和侵袭的 RhoA/ROCK 信号因子（RhoA、Rock 和 p-LIMK）水平也随着 Trio 的抑制而降低。因此，Trio 可能通过 RhoA/ROCK 信号通路调节宫颈癌的迁移和侵袭。
