Small Nuclear RNA 64 (snoRNA64): A novel Tumor Biomarker for Pancreatic Cancer

Abstract

The pancreatic ductal adenocarcinoma (PDAC), which represents over 90% of pancreatic cancer cases, has the highest proliferative and metastatic rate in comparison to other pancreatic cancer compartments. This study is designed to determine whether small nucleolar RNA, H/ACA box 64 (snoRNA64) is associated with pancreatic cancer initiation and progression. Gene expression data from the Gene Expression Omnibus (GEO) repository have shown that snoRNA64 expression is reduced in primary and metastatic pancreatic cancer as compared to normal tissues based on statistical analysis of the in Silico analysis. Using qPCR techniques, pancreatic cancer cell lines include PK-1, PK-8, PK-4, and Mia PaCa-2 with different levels of snoRNA64, including PK-1, PK-8, PK-4, and Mia PaCa-2. The level of expression is correlated with the cell line epithelial or mesenchymal characteristics. Cell lines displaying epithelial characteristics such as PK-1, PK-8 show high levels of snoRNA64 meanwhile, cell lines displaying mesenchymal characteristics such as PK-4, Mia PaCa-2 show low levels of snoRNA64. The level of expression is correlated with the cell line epithelial or mesenchymal characteristics. After knocking down the PK-8 with high snoRNA64 expression, the epithelial markers E. cadherin (E-cad) and Cytokeratin-8 (CK-8) are decreased, while mesenchymal markers Vimentin (Vim), Cytokeratin-19 (CK-19), Metalloprotease -2 (MMP-2), and Metalloprotease-3 (MMP-3) are activated. Those changes suggest that PK-8 responding to the snoRNA64 knock down protocol and increase in mesenchymal function. Together, snoRNA64 expression may participate in epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET), in which during metastasis these processes are crucial. In addition, snoRNA64 may be considered as a potential diagnostic biomarker for both early and invasive stages of PDAC. And due to its gradual expression decreases, it may be considered a barrier in tumor progression.