Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Jiangxi Institute of Urology, The First Affiliated Hospital of Nanchang University, China.
Bioengineered. 2022 Mar;13(3):5663-5674. doi: 10.1080/21655979.2022.2031671.
The GTP-binding protein Di-Ras3 (DIRAS3) has been established as a maternally imprinted tumor suppressor gene. Growing evidence has correlated the DIRAS3 gene with tumor progression, but its role in non-small cell lung cancer (NSCLC) is rarely reported. Accordingly, the current study sought to evaluate the role and mechanism of DIRAS3 in NSCLC cell progression. First, we uncovered that DIRAS3 was poorly expressed in NSCLC tissues and cells. Subsequently, we examined the effect of DIRAS3 over-expression or knockdown in different lung cancer cells on their malignant phenotypes, with the help of transwell cell migration and invasion assays, and Western blot analyses. It was found that the over-expression of DIRAS3 inhibited the migration and invasion of A549 cells or H520 cells, whereas knockdown of DIRAS3 led to opposing trends. In addition, over-expression of DIRAS3 attenuated the tumor growth and reduced the number of lung tumor nodules. Mechanistically, DIRAS3 may inhibit the migration and invasion of NSCLC cells by inhibiting the RAS/extracellular-regulated kinase (ERK) signaling pathway. Collectively, our findings indicate that DIRAS3 could serve as a potential therapeutic target biomarker for NSCLC.
GTP 结合蛋白 Di-Ras3（DIRAS3）已被确定为一种母系印迹的肿瘤抑制基因。越来越多的证据表明 DIRAS3 基因与肿瘤进展相关，但它在非小细胞肺癌（NSCLC）中的作用很少有报道。因此，本研究旨在评估 DIRAS3 在 NSCLC 细胞进展中的作用和机制。首先，我们发现在 NSCLC 组织和细胞中 DIRAS3 表达水平较低。随后，我们通过 Transwell 细胞迁移和侵袭实验以及 Western blot 分析，研究了 DIRAS3 过表达或敲低对不同肺癌细胞恶性表型的影响。结果发现，DIRAS3 的过表达抑制了 A549 细胞或 H520 细胞的迁移和侵袭，而 DIRAS3 的敲低则导致相反的趋势。此外，过表达 DIRAS3 可抑制肿瘤生长并减少肺肿瘤结节数量。从机制上讲，DIRAS3 可能通过抑制 RAS/细胞外调节激酶（ERK）信号通路抑制 NSCLC 细胞的迁移和侵袭。综上所述，我们的研究结果表明 DIRAS3 可能成为 NSCLC 的潜在治疗靶点生物标志物。
