Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Med Oncol. 2023 Sep 1;40(10):287. doi: 10.1007/s12032-023-02163-x.
Sine oculis homeobox 4 (SIX4), a critical transcription factor modulating organ development, potentially participates in tumorigenesis through numerous pathways. Here, we investigated siRNA-mediated knockdown effects of SIX4 on pancreatic cancer cells and underlying molecular mechanisms. The expression of SIX4 in pancreatic cancer and adjacent tissues were investigated in clinical tissue samples and bioinformatically approved by gene expression omnibus (GEO) database. Appropriate siRNA transfected into PANC1 pancreatic cancer cells in order to SIX4 knockdown. The survival, migration, invasion, colony formation, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle in the cancer cells were investigated after knockdown of SIX4. In addition, expression of genes involved in apoptosis and metastasis were assessed in the transfected cancer cells in mRNA and protein levels. High-throughput analysis using GEO database confirmed the overexpression of SIX4 in pancreatic cancer tissues by six independent pancreatic cancer microarrays. Knockdown of SIX4 by specific siRNA significantly decreased survival, colony formation, and mitochondrial membrane potential of the cancer cells. Further assessments demonstrated that knockdown of SIX4 increases the apoptosis and autophagy rates in the cancer cells through modifying the expression of related genes. Moreover, a significant decrease in migration and invasion rates were observed in SIX4 suppressed group. Furthermore, frequency of the cells transfected with SIX4 siRNA increased slightly in G1 and Sub-G1 phases of cell cycle. Our study suggested that siRNA-mediated knockdown of SIX4 increases the pancreatic cancer cells death and reduces the invasion and migration of the cancer cells through different molecular pathways.
Sine oculis homeobox 4 (SIX4)，一种调节器官发育的关键转录因子，可能通过多种途径参与肿瘤发生。在这里，我们研究了 SIX4 对胰腺癌细胞的 siRNA 介导敲低效应及其潜在的分子机制。在临床组织样本中研究了 SIX4 在胰腺癌和相邻组织中的表达，并通过基因表达综合数据库 (GEO) 进行了生物信息学验证。将适当的 siRNA 转染到 PANC1 胰腺癌细胞中以敲低 SIX4。敲低 SIX4 后，研究了癌细胞的存活、迁移、侵袭、集落形成、线粒体膜电位、凋亡、自噬和细胞周期。此外，还评估了转染癌细胞中参与凋亡和转移的基因在 mRNA 和蛋白水平上的表达。使用 GEO 数据库的高通量分析通过六个独立的胰腺癌微阵列证实了 SIX4 在胰腺癌组织中的过表达。特异性 siRNA 敲低 SIX4 显著降低了癌细胞的存活、集落形成和线粒体膜电位。进一步评估表明，通过修饰相关基因的表达，敲低 SIX4 增加了癌细胞的凋亡和自噬率。此外，在 SIX4 抑制组中观察到迁移和侵袭率显著降低。此外，转染 SIX4 siRNA 的细胞在细胞周期的 G1 和 Sub-G1 期的频率略有增加。我们的研究表明，siRNA 介导的 SIX4 敲低通过不同的分子途径增加了胰腺癌细胞的死亡，并降低了癌细胞的侵袭和迁移。
