RRM2 Promotes Liver Metastasis of Pancreatic Cancer by Stabilizing YBX1 and Activating the TGF-beta Pathway

Ribonucleotide reductase subunit M2 (RRM2) has been associated with various types of cancers and is related to tumor progression. However, the role of RRM2 in the liver metastasis of pancreatic cancer remains unclear. In this study, RRM2 was found to promote the malignant biological behavior of pancreatic cancer and enhance its liver metastasis. Further investigation into the downstream molecular mechanisms of RRM2 revealed that RRM2 stabilizes YBX1, upregulates TGFBR1, and activates the TGF-beta pathway to promote the progression and liver metastasis of pancreatic cancer. To further validate our hypothesis, we performed RNA sequencing under the specified conditions to determine the impact of RRM2 on downstream genes that can affect the liver metastasis of pancreatic cancer. Overall design: To explore the downstream genes regulated by RRM2, we established PANC-1 cell lines with targeted knockdown of the gene of interest using shRNA technology. We subsequently conducted a gene expression profiling analysis, utilizing data derived from RNA sequencing of two distinct cell populations: the non-targeting control cells (shNC) and those with RRM2 knockdown (shRRM2).