Cancer Biomark. 2017 Dec 6;20(4):499-509. doi: 10.3233/CBM-170324.
Gastric cancer is one of the most common malignancies worldwide. Recent studies reported that Piwil3 was overexpressed in various cancers, including gastric cancer (GC). This study was intended to investigate its function and mechanism in GC progress.
Quantitative real time PCR(RT-PCR) and western blotting assays were utilized to measure mRNA and protein expression levels, respectively. SiRNA transfection was performed to suppress the expression of Piwil3. CCK-8 assay, cell invasion and migration assays were used to determine the cell proliferative, cell invasive and migratory ability.
The expression of Piwil3 was significantly increased in GC tissues compared with matched normal tissues. The specific siRNA significantly inhibited the protein and mRNA expressions of Piwil3, and effectively inhibited the proliferation and induced G0/G1 phase arrest in GC cells. Downregulation of Piwil3 significantly suppressed the migration and invasion of GC cells. Moreover, the downregulation of Piwil3 also significantly suppressed the tumor volumes in nude mice. Mechanism investigation showed that the downregulation of Piwil3 significantly decreased the mRNA and protein expressions of metastasis-related genes, including RhoC, MTA1, MMP2 and MMP9, and also modulated the phosphorylation levels of JAK2 and STAT3 but not their protein levels.
These findings indicate that overexpression of Piwil3 promotes the proliferation, migration and invasion of GC cells partially through JAK2/STAT3 signal pathway.
胃癌是全球最常见的恶性肿瘤之一。最近的研究报告称,Piwil3 在多种癌症中过表达,包括胃癌(GC)。本研究旨在探讨其在 GC 进展中的功能和机制。
采用定量实时 PCR(RT-PCR)和 Western blot 检测分别测量 mRNA 和蛋白表达水平。采用 siRNA 转染抑制 Piwil3 的表达。CCK-8 测定、细胞侵袭和迁移实验用于确定细胞增殖、细胞侵袭和迁移能力。
与配对的正常组织相比,Piwil3 在 GC 组织中的表达明显升高。特异性 siRNA 显著抑制 Piwil3 的蛋白和 mRNA 表达,并有效抑制 GC 细胞的增殖,诱导 G0/G1 期阻滞。下调 Piwil3 显著抑制 GC 细胞的迁移和侵袭。此外,下调 Piwil3 还显著抑制裸鼠的肿瘤体积。机制研究表明,下调 Piwil3 显著降低了 RhoC、MTA1、MMP2 和 MMP9 等转移相关基因的 mRNA 和蛋白表达水平,同时调节了 JAK2/STAT3 信号通路的磷酸化水平,但不影响其蛋白水平。
这些发现表明,Piwil3 的过表达部分通过 JAK2/STAT3 信号通路促进 GC 细胞的增殖、迁移和侵袭。