Sine oculis homeobox 4 (SIX4)是一种关键的转录因子，通过多种途径参与肿瘤发生。在本研究中，我们调查了siRNA介导的SIX4对胰腺癌细胞的敲低效果以及潜在的分子机制。通过对临床组织样本的研究以及基因表达公共数据库(GEO)的验证，我们研究了胰腺癌和相邻组织中SIX4的表达情况。然后，我们将合适的siRNA转染到PANC1胰腺癌细胞中，以达到敲低SIX4的目的。在SIX4敲低后，我们研究了癌细胞的存活率、迁移率、侵袭能力、集落形成能力、线粒体膜电位、凋亡、自噬和细胞周期。此外，我们在转染的癌细胞中对参与凋亡和转移的基因的表达进行了mRNA和蛋白质水平的评估。GEO数据库的高通量分析进一步证实了六个独立胰腺癌微阵列中SIX4在胰腺癌组织中的过表达。通过特异性siRNA敲低SIX4明显降低了癌细胞的存活率、集落形成能力和线粒体膜电位。进一步的研究显示，SIX4的敲低通过调节相关基因的表达，提高了癌细胞的凋亡和自噬率。此外，SIX4敲低组中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期略有增加。我们的研究表明，通过siRNA介导的SIX4敲低，增加了胰腺癌细胞的死亡率，并通过不同的分子途径减少了癌细胞的侵袭和迁移。© 2023. 著者，独家授权给Springer Science+Business Media, LLC，Springer Nature的一部分。

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.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.